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Melanoma

A plain-English summary of the published research on Melanoma, reviewed and approved by our editors — not a hand-curated clinical overview.

Research summary · reviewed
Educational only: This page is not medical advice. Coordinate decisions with your oncology team.

Reviewed Jun 2026 · OncoForge editorial · How we review →

AI extractedhuman reviewedsources checkedretractions suppressed· last updated Jun 2026

Evidence at a glanceHuman · observationalMixed results⚠ Studies disagree
40 published studies that name Melanoma4 human studies approved & graded (trial, observational, or meta-analysis)213 human clinical studies in the Melanoma corpus1461 source documents in the Melanoma corpus

last checked June 19, 2026

Why this grade?

Human · observational — Human observational evidence only — no trials.

Computed deterministically from the studies’ types and reported outcomes — not written by AI, and not a claim that anything works.

What the guidelines say

NCI PDQESMONCCNASCO

We link the authoritative guidelines rather than reproduce them. Below, the treatments on this page are split into standard care, guideline or regulatory options, supportive care, and studied but not standard so established care is not mixed with experimental or supportive items.

Guideline / FDA options - context-specific
  • pembrolizumab
Studied, not standard - investigational
  • chemotherapy
  • Conventional chemotherapy
  • Anti-LAG-3 antibodies
  • cancer vaccine therapy
  • effector T-cell therapy
  • high-dose interferon
  • immune checkpoint inhibitors
  • Immune checkpoint inhibitors (CTLA-4/PD-1/PD-L1)
  • Interferon-α
  • interferon-alpha
  • ipilimumab
  • ipilimumab + nivolumab
  • ipilimumab or nivolumab
  • ipilimumab plus nivolumab
  • mRNA-4157/V940 plus pembrolizumab
  • nivolumab
  • nivolumab + ipilimumab
  • nivolumab plus low-dose ipilimumab
  • pucotenlimab
  • tebentafusp
  • tumor-infiltrating lymphocytes (TIL)
  • Antibiotics, proton pump inhibitors (PPIs), and probiotics
  • systemic glucocorticoids
  • systemic medical treatment
  • biopsy
  • excision with 2 mm margin
  • labial reconstruction
  • liver-directed regional therapies
  • Mohs micrographic surgery
  • sentinel lymph node dissection
  • Sentinel lymph node dissection (SLND/SLNB)
  • standard surgical excision
  • surgery
  • Surgical excision (wide local excision)
  • surgical excision with 1–2 cm margins
  • Adjuvant radiation
  • beta-blockers
  • Dabrafenib
  • dabrafenib and trametinib
  • dabrafenib plus trametinib
  • dabrafenib/trametinib
  • Dabrafenib + Trametinib
  • darovasertib (NVP-LXS196)
  • encorafenib/binimetinib
  • entinostat
  • selumetinib; trametinib
  • Trametinib
  • Vemurafenib
  • vemurafenib/cobimetinib
  • vemurafenib plus cobimetinib
  • proton therapy (SFUD)
  • proton technique with IMRT
  • multimodality treatment

Read the guidelines

Cancer-specific deep links aren’t curated yet — these search the authoritative sources for Melanoma.

Treatment map: Melanoma

Open as a full page →

Standard care plus every compound studied in the literature (each cited) and graded by evidence, organized by clinical readiness. A category, not a verdict that anything works — confirm anything here with your oncology team.

64
Interventions
0
Standard of care
40
Tested in people
0
Lab / animal
18
Named in lit.
7
Classes
Standard of care (0) Guideline option (6) Tested in people (40) Lab / animal only (0) Named in the literature (18)

Tested in people, by trial phase: phase not reported ×40

Clinical evidence
Preclinical evidence
Standard of care
Guideline option
Tested in people
Lab / animal only
Named in the literature
Surgery & procedures
—
—
6
—
5
Radiotherapy
—
—
2
—
1
Chemotherapy
—
—
1
—
1
Targeted therapy
—
—
8
—
6
Immunotherapy
—
6
19
—
4
Repurposed drugs
—
—
1
—
—
Other
—
—
3
—
1

Columns group into clinical evidence (used in, or tested on, people) and preclinical evidence (lab/animal, or only named in the literature). Cell = number of interventions; a dashed cell means none recorded there.

Established care — detail (6)
Immunotherapy
pembrolizumabRecurrent or later-line
FDA-approved for this cancer.
—Guideline option
pembrolizumabAdjuvant (after surgery)
FDA-approved for this cancer.
—Guideline option
pembrolizumabNeoadjuvant (before surgery)
FDA-approved for this cancer.
—Guideline option
pembrolizumabAdjuvant (after surgery) · BRAF wild-type cutaneous melanoma
FDA-approved for this cancer.
—Guideline option
pembrolizumabBRAF wild-type cutaneous melanoma
FDA-approved for this cancer.
—Guideline option
pembrolizumab
FDA-approved for this cancer.
—Guideline option
Investigational & adjunct compounds — detail (58)
Meta-analysis (40)
Anti-LAG-3 antibodiesAntibiotics, proton pump inhibitors (PPIs), and probioticsbeta-blockersbiopsycancer vaccine therapychemotherapydabrafenib + trametinibdabrafenib and trametinib· Adjuvant (after surgery) · BRAF-mutantdabrafenib/trametinib· BRAF-mutantdarovasertib (NVP-LXS196)effector T-cell therapyencorafenib/binimetinib· BRAF-mutantentinostathigh-dose interferon· Adjuvant (after surgery)immune checkpoint inhibitorsImmune checkpoint inhibitors (CTLA-4/PD-1/PD-L1)ipilimumabipilimumab + nivolumabipilimumab or nivolumabipilimumab plus nivolumab· BRAF wild-type cutaneous melanomaipilimumab plus nivolumab· BRAF-mutantlabial reconstructionliver-directed regional therapiesMohs micrographic surgerymRNA-4157/V940 plus pembrolizumabmultimodality treatmentnivolumab· Adjuvant (after surgery) · BRAF wild-type cutaneous melanomanivolumab· BRAF wild-type cutaneous melanomanivolumabnivolumab + ipilimumab· First-line (advanced disease)proton technique with IMRTproton therapy (SFUD)pucotenlimabselumetinib; trametinibstandard surgical excisionsurgerysystemic glucocorticoidstebentafusp· HLA-A*02:01tumor-infiltrating lymphocytes (TIL)vemurafenib/cobimetinib· BRAF-mutant
Named in the literature
Conventional chemotherapyInterferon-α· Adjuvant (after surgery)interferon-alpha· Adjuvant (after surgery)nivolumab· Adjuvant (after surgery)nivolumab plus low-dose ipilimumab· Adjuvant (after surgery)systemic medical treatmentexcision with 2 mm marginsentinel lymph node dissectionSentinel lymph node dissection (SLND/SLNB)Surgical excision (wide local excision)surgical excision with 1–2 cm marginsAdjuvant radiation· Adjuvant (after surgery)Dabrafenib· BRAF V600 mutationsdabrafenib plus trametinib· Adjuvant (after surgery) · BRAF-mutated melanomaDabrafenib + Trametinib· BRAF V600 mutationsTrametinib· BRAF V600 mutationsVemurafenib· BRAF mutatedvemurafenib plus cobimetinib· BRAF-mutated melanoma

"Tested in people" rows show the highest trial phase found in that compound's cited human studies (Phase I–IV; "phase not reported" = a human study with no phase tag). "Studied" = named in the cited literature for this cancer. "FDA ✓" = FDA-approved for this cancer; "off-label" = an FDA-approved drug used outside its approved indications (per openFDA). Not a claim that anything works.

Reported figures

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Snapshot

The essentials in ~60 seconds — every line is drawn from the cited sources below.

What it is
Cutaneous melanoma is a malignant tumour arising from neural crest–derived skin melanocytes; diagnosis is clinical and staging uses the AJCC system. [1][2][3]
Survival
Worldwide there are over 330,000 new cases and more than 58,000 deaths each year; in the United States about 13,120 deaths were projected in 2024. [1][4][5]
Standard treatment
Surgery is the primary treatment for early-stage disease (excision with 1–2 cm margins and sentinel lymph node biopsy for tumours >1 mm); in advanced or unresectable disease systemic options include immunotherapy and targeted therapy, with multidisciplinary (NCCN) guidance. [6][2][1][7][3][8]
Key test
BRAF V600 mutation testing (mandatory in stage IV) — used to guide systemic therapy and to select targeted combinations such as dabrafenib plus trametinib for unresectable/metastatic disease. [1][9][7]
Biggest challenge
A major challenge is loss of response or resistance to existing immunotherapies and targeted therapies, leaving limited options for some patients; late-stage complications such as leptomeningeal disease carry very poor prognosis. [4][10][11]

Ask about Melanoma

Answers come only from the cited sources on this page — with the supporting evidence shown. If the sources here don't cover your question, it will say so. Educational information, not medical advice.

Key numbers & factors

Risk factors

  • ▲ increases riskUltraviolet radiation (sunlight and/or indoor tanning) [1][2]
  • ▲ increases riskPTEN hamartoma tumor syndrome (PHTS) — PHTS affects approximately 1 in 200,000 to 250,000 people [12]
  • ▼ lowers riskAlopecia areata — Reported associations include OR 0.10 (95% CI, 0.02-0.44) and HR 0.53 (95% CI, 0.34-0.83); pooled OR 0.58 (95% CI, 0.27-1.22; p = 0.12) [13]
  • ▼ lowers riskVitiligo [14]

Biomarkers

  • BRAF V600ActionableGuides systemic targeted therapy selection in adjuvant and unresectable/metastatic settings (e.g., dabrafenib + trametinib) [9][7][1]
  • PD-L1 expression · Reported predictive value inconsistent; not mandatory for stage IV because negative patients may still respond to anti‑PD‑1 [1][10]
  • ATP5B · Prognostic association — higher expression linked with poorer overall survival across pooled solid‑tumour studies [15]
  • CDKN2A · Major familial melanoma susceptibility gene [2]
  • C-KIT and NRAS · Optional mutation testing in stage IV [1]
  • S-100, SOX-10, HMB-45, PRAME, MART-1 · Commonly used immunohistochemistry markers to help diagnose melanoma [1]

10 sections — tap any heading to expand its cited detail. Key points are above.

Overview14 points

Key figures

Survival & outcomes
OutcomeValue95% CI
percentage of skin cancer mortality90%—
Source quotes
  • “Cutaneous melanoma (CM) is potentially the most dangerous form of skin tumour and causes 90% of skin cancer mortality.”
  • Sources describe that immune checkpoint inhibitors such as nivolumab and ipilimumab have improved survival in advanced melanoma, though resistance can occur; immunotherapy and targeted therapies have helped many patients with advanced disease live longer. [10][16][17][4]4 sources
  • Cutaneous melanoma is described as the most serious or potentially most dangerous form of skin tumor and is responsible for most skin cancer mortality (reported as causing 90% of skin cancer mortality). [3][8][4]3 sources
  • Cutaneous melanoma is a malignant tumor arising from neural crest–derived cutaneous melanocytes; up to 90% of melanomas originate from skin melanocytes. [1][2]
  • Diagnosis is made clinically and staging is based upon the AJCC system. [3]
  • Ultraviolet radiation (sunlight and/or indoor tanning) is the main risk factor for melanoma and is implicated in the increasing incidence. [1]
  • Globally, over 330,000 melanoma skin cancers are estimated to occur each year and the incidence of skin cancer is increasing. [18]
  • In the United States, recent data projected that in 2024 about 108,270 people would be diagnosed with skin cancer and 13,120 would die from the disease. [5]
  • The NCCN Guidelines for Melanoma provide multidisciplinary recommendations for the management of patients with melanoma. [7]
  • Melanoma was one of the most commonly studied cancer types in the literature on cutaneous immune-related adverse events (cirAEs). [19]
  • Cutaneous melanoma is described as a potentially life‑shortening condition and is the fifth most common cancer in the United Kingdom. [20]
  • Lip melanoma is a rare malignant neoplasm arising at the cutaneous–mucosal interface. [21]
  • Patients with PTEN hamartoma tumor syndrome (PHTS) have a higher predisposition to melanoma. [12]
  • Pregnancy-associated melanoma (PAM) is defined as melanoma diagnosed during pregnancy or within 12 months postpartum. [22]
  • Leptomeningeal disease (LMD) is an increasingly recognised late-stage complication of solid tumours, primarily including melanoma. [11]
Epidemiology16 points

Key figures

Survival & outcomes
OutcomeValue95% CI
deaths per year58000—
proportion linked to UVR86%—
proportion of skin cancer mortality caused by cutaneous melanoma90%—
male_proportion71.2%—
mean_age51.1—
lower_lip_proportion63.8%—
meta-analysis effect size for change in Breslow thickness (post- vs pre-COVID)0.08—
Prognostic factors
FactorEffectHR (95% CI)p
melanoma OR (Conic et al.)▼ better0.1 (0.02–0.44)< 0.001
invasive melanoma HR (Delcoigne et al.)▼ better0.53 (0.34–0.83)—
overall skin cancer OR▼ better0.58 (0.27–1.22)= 0.12
risk ratio for ulceration post-COVID vs pre-COVID▲ worse1.31—
Source quotes
  • “The number of cases is rising, especially among people with fair skin in developed countries, with over 330,000 new cases and more than 58,000 deaths worldwide each year.”
  • “It is estimated that around 86 per cent of melanomas in the UK in 2010 were linked to exposure to UVR from the sun and sun-beds.”
  • “Cutaneous melanoma (CM) is potentially the most dangerous form of skin tumour and causes 90% of skin cancer mortality.”
  • “Individuals were predominantly male (71.2%), with a mean age of 51.1years.”
  • “Most lesions involved the lower lip (63.8%) and presented clinically as pigmented, nodular, and frequently ulcerated lesions; approximately 8% were amelanotic.”
  • “studies show a rising trend in the Breslow index post-COVID, but less significantly, with an effect size of 0.08 regarding the meta-analysis model (P=0.02) with a pre-COVID mean Breslow of 1.56mm and post-COVID of 1.84mm.”
  • “Conic et al. found significantly reduced incidence of melanoma (OR 0.10; 95% CI, 0.02-0.44), BCC (OR 0.14; 95% CI, 0.09-0.22), and SCC (OR 0.22; 95% CI, 0.12-0.42) (all p < 0.001) (20).”
  • “Delcoigne et al. demonstrated lower hazards for invasive melanoma (HR 0.53; 95% CI, 0.34-0.83), melanoma in situ (HR 0.81; 95% CI, 0.56-1.16), SCC (HR 0.65; 95% CI, 0.43-0.98), and SCC in situ (HR 0.89; 95% CI, 0.64-1.23) (22).”
  • “Patients with AA demonstrated lower odds compared with controls, though the result did not reach statistical significance (OR 0.58; 95% CI, 0.27-1.22; p = 0.12) (Figure 2).”
  • “post-COVID ulceration surpassed pre-COVID levels significantly, with a risk ratio of 1.31 and an estimated odds ratio of 1.41, indicating a 44% rise post-COVID.”
  • Sources report over 330,000 new cutaneous melanoma cases and more than 58,000 deaths worldwide each year. [1][4]
  • A systematic review of lip melanoma (43 studies, 139 individuals) found cases were predominantly male (71.2%), with a mean age of 51.1 years, and most lesions involved the lower lip (63.8%). [21]
  • The incidence of melanoma has been increasing rapidly in most parts of the world over the last few decades. [2]
  • In the UK, around 86% of melanomas in 2010 were linked to exposure to ultraviolet radiation (UVR), and the male:female ratio for melanoma cases was reported as 10:11. [2]
  • In 10–20% of patients with regional or visceral melanoma metastases the primary melanoma is never found (melanoma of unknown primary). [2]
  • Cutaneous melanoma accounts for 90% of skin cancer deaths. [8]
  • Staging and diagnosis of cutaneous melanoma are guided by clinical evaluation and the American Joint Committee on Cancer (AJCC) staging system. [8]
  • Non-melanoma skin cancer, including basal and squamous cell carcinoma, represents the most common malignancy. [23]
  • In South Africa melanoma remains a common cancer and, despite earlier diagnosis, at least 850 people continue to die of melanoma each year. [24]
  • In a systematic review of sinonasal tumours, sinonasal mucosal melanoma (SNMM) comprised 3,527 cases, representing 12.1% of the dataset. [25]
  • PTEN hamartoma tumor syndrome (PHTS) affects approximately 1 in 200,000 to 250,000 people worldwide. [12]
  • A lower incidence of melanoma has been reported in patients with vitiligo. [14]
  • Studies of alopecia areata report mixed effects on skin cancer risk: several large population-based studies found significantly decreased incidence of melanoma and non-melanoma skin cancer, including Conic et al. (OR 0.10; 95% CI, 0.02-0.44) and Delcoigne et al. (HR 0.53; 95% CI, 0.34-0.83), while a pooled analysis suggested lower odds overall that did not reach statistical significance (OR 0.58; 95% CI, 0.27-1.22; p = 0.12). [13]
  • A meta-analysis found post-COVID ulceration rates in melanoma were higher than pre-COVID (risk ratio 1.31; estimated odds ratio 1.41) and reported a small but statistically significant increase in Breslow thickness (meta-analysis effect size 0.08, P = 0.02), with mean Breslow thickness rising from 1.56 mm pre-COVID to 1.84 mm post-COVID. [26]
  • A 2026 systematic review and meta-analysis of Mendelian randomization studies of type 2 diabetes and cancer included melanoma among the 17 cancer types investigated. [27]
  • The PAM meta-analysis identified 11 studies for qualitative synthesis and meta-analysed 3 low-risk-of-bias studies comprising 16,467 women including 1,662 with PAM. [22]
Key biomarkers8 points
  • BRAF mutation status is used to guide systemic therapy choices in adjuvant and unresectable/metastatic settings for cutaneous melanoma, and BRAF V600 mutations are used to select systemic targeted options such as dabrafenib and trametinib for patients with unresectable metastatic melanoma. [9][7]
  • The most frequently mutated genes in both primary and metastatic cutaneous melanoma were BRAF, TERT, TP53, NRAS, and NF1, with BRAF the most frequent mutation occurring in nearly 40% of cases in the pooled data; the prevalence of BRAF, NRAS, TERT, CDKN2A, and PTEN mutations was significantly higher in metastatic lesions than in primary tumors; and acral melanoma exhibited a distinct molecular profile with an overall lower mutation prevalence, particularly involving BRAF. [4]
  • For stage IV melanoma, determination of BRAF V600 status is mandatory; determination of C-KIT and NRAS status is optional; and immunohistochemical determination of programmed death ligand 1 (PD-L1) is not mandatory because patients with negative expression may respond to anti-PD1 antibodies. [1]
  • The predictive values of biomarkers such as PD-L1 expression, KMT2D mutation, and NLR have been reported as inconsistent across studies. [10]
  • ATP5B (mitochondrial ATP synthase F1 subunit beta) is involved in the catalytic process of oxidative phosphorylation (OXPHOS); across pooled studies of solid tumors, high ATP5B expression was significantly associated with poorer overall survival (HR = 1.95, 95%CI: 1.29-2.94), and in subgroup analyses the meta-analysis reported reduced heterogeneity in the melanoma subgroup (I = 44%). [15]
  • The CDKN2A gene is the major melanoma susceptibility gene identified to date in familial melanoma cases. [2]
  • Some modelling studies and reviews included patient groups described as having BRAF-mutant melanoma. [18]
  • Mucocutaneous manifestations are often among the earliest signs of PHTS. [12]
Biology & pathways9 points
  • Several proteins are commonly used as markers for melanoma in immunohistochemistry testing, including S-100 protein, SOX-10, HMB-45, PRAME, and MART-1. [1]
  • Tumour-specific mRNA vaccines encode personalised neoantigens and are being developed in combination with immune checkpoint inhibitors for oncology applications including melanoma. [28]
  • ATP5B is involved in the catalytic process of oxidative phosphorylation (OXPHOS). [15]
  • PD-1 expression on antigen-stimulated T cells inhibits activation, proliferation, and cytokine secretion and may remain high in tumors, contributing to T cell exhaustion. [6]
  • CTLA-4 is expressed by regulatory T cells and acts as a competitive antagonist to CD28–CD80/86 binding, impeding T cell initiation and activation. [6]
  • Factors that influence the gut microbiome may play a critical role in the effectiveness of cancer immunotherapies, particularly immune checkpoint inhibitors. [29]
  • A Mendelian randomization analysis treated skin microbiota as exposures and melanoma as an outcome to explore potential causal relationships. [5]
  • PHTS is caused by germline pathogenic variants in the tumor suppressor PTEN gene. [12]
  • The authors propose hypotheses on underlying mechanisms that include both immune-mediated and nonimmune-mediated pathways. [14]
Standard management16 points
  • Sources note that sentinel lymph node biopsy is a staging procedure routinely offered for melanomas more than 1 mm in thickness. [1][3][8][2]4 sources
  • Sources state that histological examination after biopsy is essential to confirm the diagnosis and that excisional biopsy is the method of choice. [1][2][20]3 sources
  • For patients with a positive sentinel lymph node biopsy, completion (complete) lymph node dissection can carry morbidity and has not been shown to improve survival (no clear resultant survival benefit). [1][3][8]3 sources
  • In distant or advanced metastatic disease, systemic medical treatment is indicated when surgical options are not feasible; available approaches include immunotherapy, targeted therapy, and chemotherapy, although historically systemic treatments have yielded low response rates. [6][3][8]3 sources
  • Sources state that melanomas are excised with 1–2 cm safety margins, with at least 1 cm and up to 3 cm depending on tumour thickness and anatomical site. [2][8]
  • Artificial intelligence and deep learning methods have shown high accuracy on benchmark datasets and demonstrate potential for skin cancer diagnosis, but they face important limitations, including class imbalance and limited clinical validation. [30][31]
  • A full body skin check by an experienced dermatologist and a complete physical examination are recommended for all patients diagnosed with melanoma at any stage. [1]
  • Surgical intervention remains the primary treatment for early-stage melanoma. [6]
  • Therapeutic decisions in stage IV patients should be primarily made by an interdisciplinary oncology team (tumour board). [8]
  • Adjuvant interferon-alpha can be offered for patients with tumours >1.5 mm thickness and stage II–III melanoma because it increases relapse-free survival. [3]
  • Patients with mucosal melanoma may be offered the same therapies recommended for cutaneous melanoma. [9]
  • Early detection is associated with lower morbidity and mortality; observational studies have indicated a decrease in mortality risk associated with routine skin checks, but large randomized controlled trials have not been conducted. [18]
  • Researchers have studied whether the time of day of immune checkpoint inhibitor (ICI) administration is associated with oncologic outcomes such as overall survival and progression-free survival. [16]
  • Dermatologists play a role in early recognition and diagnosis that can enable timely cancer screening and management. [12]
  • Leptomeningeal disease (LMD) carries a poor prognosis with reported survival ranging from 2 to 6 months. [11]
  • Diagnosis and treatment of sinonasal cancers are described as requiring an interdisciplinary approach and multimodality treatment. [32]
Treatments & compounds studied68 treatments

Chemotherapy

  • chemotherapy: Sources report that, compared with conventional systemic chemotherapy, regional liver-directed therapy showed more favorable overall and progression-free survival in metastatic uveal melanoma. [33][34]
  • Conventional chemotherapy: Conventional chemotherapy is described as a systemic therapeutic comparator to newer agents in metastatic melanoma. [8]

Targeted therapy

  • Dabrafenib: BRAF V600 mutationsDabrafenib has been added as a systemic targeted option for patients with unresectable metastatic melanoma harboring BRAF V600 mutations. [7]
  • dabrafenib and trametinib: Adjuvant (after surgery) · BRAF-mutantIn the adjuvant setting, the combination of dabrafenib and trametinib should be offered in BRAF-mutant disease. [9]
  • dabrafenib plus trametinib: Adjuvant (after surgery) · BRAF-mutated melanomaIn the COMBI-AD trial, one year of adjuvant dabrafenib plus trametinib improved relapse-free survival and distant metastasis-free survival compared with placebo in patients with resected stage III BRAF-mutated melanoma. [1]
    HR for RFS 0.55 (95% CI 0.44–0.7) vs placebo
    Source quote
    • “HR 0.55 (0.44–0.7)”
  • dabrafenib/trametinib · 3 findings
    • BRAF-mutantIn the unresectable/metastatic setting, combination BRAF/MEK inhibitor therapy with dabrafenib/trametinib should be offered in BRAF-mutant disease. [9]
    • BRAF V600 mutationsDabrafenib and trametinib, either as monotherapy or combination therapy, have been added as systemic options for patients with unresectable metastatic melanoma harboring BRAF V600 mutations. [7]
    • Dabrafenib plus trametinib (for patients with BRAF V600 mutations) was reported in a randomized trial as active with controllable safety and described as improving clinical prognosis. [6]
  • darovasertib (NVP-LXS196): Darovasertib (NVP-LXS196), a pan‑PKC inhibitor, has been identified and is currently under clinical investigation for uveal melanoma. [33]
  • encorafenib/binimetinib: BRAF-mutantIn the unresectable/metastatic setting, combination BRAF/MEK inhibitor therapy with encorafenib/binimetinib should be offered in BRAF-mutant disease. [9]
  • selumetinib; trametinib: MEK inhibitors such as selumetinib and trametinib showed initial efficacy in trials for uveal melanoma but failed to improve overall survival because of acquired resistance. [33]
  • Trametinib: BRAF V600 mutationsTrametinib is listed as a systemic targeted option for patients with unresectable metastatic melanoma harboring BRAF V600 mutations, either as monotherapy or in combination with dabrafenib. [7]
  • Vemurafenib: BRAF mutatedVemurafenib is cited as a BRAF inhibitor option for BRAF mutated patients as a systemic therapeutic option apart from conventional chemotherapy. [8]
  • vemurafenib/cobimetinib: BRAF-mutantIn the unresectable/metastatic setting, combination BRAF/MEK inhibitor therapy with vemurafenib/cobimetinib is described as an option for patients with BRAF-mutant disease. [9]
  • vemurafenib plus cobimetinib: BRAF-mutated melanomaThe CO-BRIM trial evaluated vemurafenib plus cobimetinib and reported increased progression-free survival and overall survival compared with vemurafenib monotherapy in BRAF-mutated melanoma. [1]
Show 1 lab & early-research entry
  • entinostat: The HDAC inhibitor entinostat has been reported to induce apoptosis and revert uveal melanoma cells to a differentiated, melanocytic gene expression profile and is a focus of research. [33]

Immunotherapy

  • Anti-LAG-3 antibodies: A systematic review and meta-analysis evaluated anti-LAG-3 antibodies in melanoma and reported pooled efficacy endpoints and pooled rates of treatment-related adverse events including 66% any-grade treatment-related adverse events and 19% grade ≥ 3 treatment-related adverse events. [17]
    any-grade treatment-related adverse events (trAEs) 66% (95% CI 51–81)grade ≥3 treatment-related adverse events (trAEs) 19% (95% CI 11–27)any-grade AEs leading to discontinuation 12% (95% CI 9–14)grade ≥3 AEs leading to discontinuation 8% (95% CI 6–10)any-grade overall adverse events 76% (95% CI 34–100)grade ≥3 overall adverse events 33% (95% CI 15–50)
    Source quotes
    • “Our analysis showed 66% of any grade treatment-related adverse events (trAEs) (95% CI: 51%-81%), 19% of grade ≥ 3 trAEs (95% CI: 11%- 27%), 12% of any grade AEs leading to discontinuation (95% CI: 9%-14%), and 8% of grade ≥ 3 AEs leading to discontinuation (95% CI: 6%- 10%).”
    • “Our analysis showed 66% of any grade treatment-related adverse events (trAEs) (95% CI: 51%-81%), 19% of grade ≥ 3 trAEs (95% CI: 11%- 27%), 12% of any grade AEs leading to discontinuation (95% CI: 9%-14%), and 8% of grade ≥ 3 AEs leading to discontinuation (95% CI: 6%- 10%).”
    • “Our analysis showed 66% of any grade treatment-related adverse events (trAEs) (95% CI: 51%-81%), 19% of grade ≥ 3 trAEs (95% CI: 11%- 27%), 12% of any grade AEs leading to discontinuation (95% CI: 9%-14%), and 8% of grade ≥ 3 AEs leading to discontinuation (95% CI: 6%- 10%).”
    • “Our analysis showed 66% of any grade treatment-related adverse events (trAEs) (95% CI: 51%-81%), 19% of grade ≥ 3 trAEs (95% CI: 11%- 27%), 12% of any grade AEs leading to discontinuation (95% CI: 9%-14%), and 8% of grade ≥ 3 AEs leading to discontinuation (95% CI: 6%- 10%).”
    • “76% of any grade overall AEs (95% CI: 34%-100%), and 33% of grade ≥ 3 overall AEs (95% CI: 15%-50%).”
    • “76% of any grade overall AEs (95% CI: 34%-100%), and 33% of grade ≥ 3 overall AEs (95% CI: 15%-50%).”
  • cancer vaccine therapy: Cancer vaccine therapy did not show a statistically significant improvement in overall survival, progression-free survival, disease-free survival, or recurrence-free survival and did not significantly increase adverse events in pooled randomized trials. [34]
    pooled RR for overall survival at 12 months 1.11 (95% CI 0.97–1.32) vs controlpooled risk difference for overall survival at 12 months 0.02 vs control
    Source quotes
    • “For the primary outcome, OS, the pooled RR was 1.11 (95% CI, 0.97-1.32, I2=59.0%), and the pooled RD was 0.02 (-0.01 to 0.06, I2=74.0%) at 12months.”
    • “For the primary outcome, OS, the pooled RR was 1.11 (95% CI, 0.97-1.32, I2=59.0%), and the pooled RD was 0.02 (-0.01 to 0.06, I2=74.0%) at 12months.”
  • effector T-cell therapy: A literature search identified 44 studies on effector T-cell therapy in the context of malignant melanoma research considered in the vaccine/systematic review. [34]
  • high-dose interferon: Adjuvant (after surgery)High-dose interferon has been modelled as an adjuvant therapy for melanoma in cost-effectiveness and simulation studies. [18]
  • immune checkpoint inhibitors: The authors of a vaccine-focused review noted that immunotherapy as a category includes immune checkpoint inhibitors and cancer vaccine therapy and commented that their efficacy remains limited. [34]
  • Immune checkpoint inhibitors (CTLA-4/PD-1/PD-L1): Immune checkpoint inhibitors (including CTLA-4, PD-1, PD-L1 and LAG-3 inhibitors) were the exposure of interest in pooled safety analyses of clinical trials. [35]
  • Interferon-α: Adjuvant (after surgery)Interferon-α treatment may be offered to patients with stage II and III melanoma as an adjuvant therapy, with at least increases in disease-free survival and less clear effects on overall survival. [8]
  • interferon-alpha: Adjuvant (after surgery)Interferon-alpha can be offered as adjuvant therapy for patients with more than 1.5 mm thickness and stage II–III melanoma because it increases relapse-free survival (interferon-alpha). [3]
  • ipilimumab: Ipilimumab was the comparator arm versus nivolumab in CHECKMATE 238 for resected stage IIIB–IV melanoma. [1][8][16][6]4 sources
    median PFS 2.9 months (95% CI 2.8–3.2) vs nivolumab + ipilimumab and nivolumab alone
    Source quote
    • “median progression-free survival of the nivolumab plus ipilimumab group was 11.5 months (95% CI 8.7–19.3), whereas that of the nivolumab group was 6.9 months (5.1–10.2), and that of the ipilimumab group was 2.9 months (2.8–3.2)”
  • ipilimumab + nivolumab: The combination of ipilimumab plus nivolumab was used in melanoma cohorts examined in time-of-day studies. [16]
  • ipilimumab or nivolumab: Immune checkpoint inhibitors (such as ipilimumab or nivolumab) in metastatic uveal melanoma have been reported to yield low objective response rates of 10% to 18% and an uncertain survival benefit. [33]
  • ipilimumab plus nivolumab · 2 findings
    • BRAF wild-type cutaneous melanomaIn the unresectable/metastatic setting, the combination of ipilimumab plus nivolumab should be offered to patients with BRAF wild-type cutaneous melanoma. [9]
    • BRAF-mutantIn the unresectable/metastatic setting, ipilimumab plus nivolumab, nivolumab alone, or pembrolizumab alone should be offered in BRAF-mutant disease. [9]
  • mRNA-4157/V940 plus pembrolizumab: mRNA-4157/V940 plus pembrolizumab reduced melanoma recurrence or death by approximately 49% in a phase 2b trial (mRNA-4157/V940 plus pembrolizumab). [28]
    reduction in recurrence or death 49% vs pembrolizumab alone
    Source quote
    • “mRNA-4157/V940 plus pembrolizumab reduced melanoma recurrence or death by approximately 49% in phase 2b; phase-3 trials are underway.”
  • nivolumab · 7 findings
    • Nivolumab was one of the PD-1 inhibitors included in melanoma cohorts evaluated in time-of-day analyses. [16][6]
      median PFS 6.9 months (95% CI 5.1–10.2) vs nivolumab + ipilimumab and ipilimumab alone
      Source quote
      • “median progression-free survival of the nivolumab plus ipilimumab group was 11.5 months (95% CI 8.7–19.3), whereas that of the nivolumab group was 6.9 months (5.1–10.2), and that of the ipilimumab group was 2.9 months (2.8–3.2)”
    • Adjuvant (after surgery)In CHECKMATE 238, adjuvant nivolumab improved relapse-free survival compared with ipilimumab in patients with resected stage IIIB–IV melanoma. [1]
      HR for RFS 0.72 (95% CI 0.6–0.86) vs ipilimumabHR for RFS 0.42 (95% CI 0.3–0.59) vs placebo
      Source quotes
      • “HR 0.72 (0.60‒0.86)”
      • “HR 0.42 (0.30–0.59)”
    • First-line (advanced disease)Nivolumab plus ipilimumab as first-line therapy for advanced melanoma had a median progression-free survival of 11.5 months (95% CI 8.7–19.3) in the cited randomized data. [6]
      median PFS 11.5 months (95% CI 8.7–19.3) vs nivolumab alone and ipilimumab alone
      Source quote
      • “median progression-free survival of the nivolumab plus ipilimumab group was 11.5 months (95% CI 8.7–19.3), whereas that of the nivolumab group was 6.9 months (5.1–10.2), and that of the ipilimumab group was 2.9 months (2.8–3.2)”
    • Adjuvant (after surgery) · BRAF wild-type cutaneous melanomaIn the adjuvant setting, nivolumab should be offered to patients with resected stage IIIA/B/C/D BRAF wild-type cutaneous melanoma. [9]
    • BRAF wild-type cutaneous melanomaIn the unresectable/metastatic setting, nivolumab alone should be offered to patients with BRAF wild-type cutaneous melanoma. [9]
    • Adjuvant (after surgery)Combination nivolumab plus low-dose ipilimumab cannot be recommended in the adjuvant setting because a trial did not show an improvement in disease-free survival compared with nivolumab alone. [1]
    • Combined intrathecal (IT) and intravenous (IV) nivolumab was used in melanoma LMD and was reported as feasible with manageable toxicity. [11]
  • pembrolizumab · 6 findings
    • Recurrent or later-linePembrolizumab improved relapse-free survival and distant metastasis-free survival versus placebo in patients with resected stage III melanoma. [1]
      HR for RFS 0.59 (95% CI 0.49–0.7) vs placebo
      Source quote
      • “HR 0.59 (0.49–0.70)”
    • Adjuvant (after surgery)One-year adjuvant pembrolizumab improved relapse-free survival compared with placebo in patients with resected stage IIB–IIC melanoma in KEYNOTE-716. [1]
      HR for RFS 0.64 (95% CI 0.5–0.84) vs placebo
      Source quote
      • “HR 0.64 (0.50–0.84)”
    • Neoadjuvant (before surgery)Neoadjuvant pembrolizumab followed by surgery and completion pembrolizumab up to one year resulted in higher event-free survival at 2 years compared with surgery followed by pembrolizumab in resectable stage IIIB–IV melanoma in SWOG1801. [1]
      Event-free survival at 2 years 72 vs 49% (95% CI 64–80) vs surgery followed by pembrolizumab (adjuvant)
      Source quote
      • “event-free survival at 2 years was 72% (CI 64–80) in the neoadjuvant-adjuvant group versus 49% (CI 41–59) in the control-adjuvant group.”
    • Adjuvant (after surgery) · BRAF wild-type cutaneous melanomaIn the adjuvant setting, pembrolizumab should be offered to patients with resected stage IIIA/B/C/D BRAF wild-type cutaneous melanoma. [9]
    • BRAF wild-type cutaneous melanomaIn the unresectable/metastatic setting, pembrolizumab alone should be offered to patients with BRAF wild-type cutaneous melanoma. [9]
    • Pembrolizumab was reported as an ICI agent included among melanoma cohorts in the time-of-day immunotherapy studies. [16]
  • pucotenlimab: Pucotenlimab (HX008) is a humanized IgG4 anti-PD-1 monoclonal antibody that has been studied across multiple solid tumours and treatment regimens, with melanoma included among tumor types in the analyses. [10]
  • tebentafusp: HLA-A*02:01Tebentafusp, a bispecific T-cell engager for metastatic uveal melanoma, was associated with a median overall survival of 21.7 months versus 16.0 months in the control group and a hazard ratio for death of 0.51 in the cited phase III trial. [33]
    median overall survival (tebentafusp arm) 21.7 months vs control (chemotherapy or ICI monotherapy)hazard ratio for death (tebentafusp vs control) 0.51 vs control (chemotherapy or ICI monotherapy)
    Source quotes
    • “The median overall survival was 21.7 months in the tebentafusp group versus 16.0 months in the control group (hazard ratio for death, 0.51) (10).”
    • “The median overall survival was 21.7 months in the tebentafusp group versus 16.0 months in the control group (hazard ratio for death, 0.51) (10).”
  • tumor-infiltrating lymphocytes (TIL): Tumor-infiltrating lymphocyte (TIL) therapy in advanced cutaneous melanoma has produced sustained clinical responses and is noted as a potential translational approach for metastatic uveal melanoma. [33]

Radiotherapy

  • Adjuvant radiation: Adjuvant (after surgery)Adjuvant radiation is listed as a consideration following lymphadenectomy for stage III melanoma with clinically positive nodes or recurrent disease, with ongoing controversy about its value. [7]
  • proton therapy (SFUD): Proton technique with SFUD was used in a subset of non-surgical cases: 20 cases with proton technique and SFUD were reported among 62 cases treated without surgery. [32]
    cases treated only surgically 772 vs 3824 vs of total casescases treated with proton technique and SFUD 20 vs 3824 vs of total casescases treated with proton technique and IMRT 42 vs 3824 vs of total casescases treated with multimodality treatment 2990 vs 3824 vs of total cases
    Source quotes
    • “All 772 cases of total 3824 were treated only surgically.”
    • “All 62 cases of total 3824 were treated without surgery, 20 cases with proton technique and SFUD, and 42 cases with proton technique and IMRT.”
    • “All 62 cases of total 3824 were treated without surgery, 20 cases with proton technique and SFUD, and 42 cases with proton technique and IMRT.”
    • “The other 2990 cases of total 3824 were treated with multimodality treatment.”
  • proton technique with IMRT: Proton technique with IMRT was used in a subset of non-surgical cases: 42 cases with proton technique and IMRT were reported among 62 cases treated without surgery. [32]
    cases treated only surgically 772 vs 3824 vs of total casescases treated with proton technique and SFUD 20 vs 3824 vs of total casescases treated with proton technique and IMRT 42 vs 3824 vs of total casescases treated with multimodality treatment 2990 vs 3824 vs of total cases
    Source quotes
    • “All 772 cases of total 3824 were treated only surgically.”
    • “All 62 cases of total 3824 were treated without surgery, 20 cases with proton technique and SFUD, and 42 cases with proton technique and IMRT.”
    • “All 62 cases of total 3824 were treated without surgery, 20 cases with proton technique and SFUD, and 42 cases with proton technique and IMRT.”
    • “The other 2990 cases of total 3824 were treated with multimodality treatment.”

Repurposed drugs

  • beta-blockers: Beta-blocker use was associated with a benefit for disease-free survival in a pooled review of observational studies but showed no other significant association for melanoma-specific or overall survival. [36]

Procedures & devices

  • biopsy: Biopsy is the procedure identified as the definitive diagnostic standard for melanoma. [20]
  • excision with 2 mm margin: Excision with a 2 mm margin is described as adequate for pigmented lesion excision in the guideline on melanoma management. [24]
  • labial reconstruction: Surgery for lip melanoma often required labial reconstruction. [21]
  • liver-directed regional therapies: Liver-directed regional therapies for liver‑predominant metastatic uveal melanoma were associated in a meta-analysis with a median PFS of 5.2 months and median OS of 14.6 months versus systemic therapy median PFS 2.8 months and median OS 9.3 months. [33]
    median PFS (LDT) 5.2 vs 2.8 months vs systemic therapymedian OS (LDT) 14.6 vs 9.3 months vs systemic therapy
    Source quotes
    • “A meta-analysis of trials published between 2000 and 2015 indicated that liver-directed regional therapies were associated with significantly improved progression-free survival (median PFS 5.2 months) and overall survival (median OS 14.6 months) compared to systemic therapy (median PFS 2.8 months, median OS 9.3 months), independent of prognostic characteristics (4).”
    • “A meta-analysis of trials published between 2000 and 2015 indicated that liver-directed regional therapies were associated with significantly improved progression-free survival (median PFS 5.2 months) and overall survival (median OS 14.6 months) compared to systemic therapy (median PFS 2.8 months, median OS 9.3 months), independent of prognostic characteristics (4).”
  • Mohs micrographic surgery: Mohs micrographic surgery and staged surgical excisions are described as primary methods for melanoma resection. [37]
  • sentinel lymph node dissection: Sentinel lymph node dissection is routinely offered as a staging procedure in patients with tumours more than 1 mm in thickness, although there is as yet no resultant survival benefit (sentinel lymph node dissection). [3]
  • Sentinel lymph node dissection (SLND/SLNB): Sentinel lymph node dissection (SLND/SLNB) is routinely offered as a staging procedure in patients with tumours more than 1mm in thickness, although there is as yet no clear survival benefit for this approach. [8]
  • standard surgical excision: The source describes Mohs micrographic surgery and staged surgical excisions as primary methods for melanoma resection. [37]
  • surgery · 2 findings
    • Surgery was reported as the sole treatment in a subset of cases: all 772 cases of the total 3824 were treated only surgically. [32]
      cases treated only surgically 772 vs 3824 vs of total casescases treated with proton technique and SFUD 20 vs 3824 vs of total casescases treated with proton technique and IMRT 42 vs 3824 vs of total casescases treated with multimodality treatment 2990 vs 3824 vs of total cases
      Source quotes
      • “All 772 cases of total 3824 were treated only surgically.”
      • “All 62 cases of total 3824 were treated without surgery, 20 cases with proton technique and SFUD, and 42 cases with proton technique and IMRT.”
      • “All 62 cases of total 3824 were treated without surgery, 20 cases with proton technique and SFUD, and 42 cases with proton technique and IMRT.”
      • “The other 2990 cases of total 3824 were treated with multimodality treatment.”
    • Surgery was the mainstay therapeutic modality for lip melanoma. [21]
  • Surgical excision (wide local excision): Surgical excision (wide local excision) with one- to two-centimetre safety margins is used to treat cutaneous melanoma. [8]
  • surgical excision with 1–2 cm margins: CMs are excised with one to two centimetre safety margins (surgical excision). [3]

Other

  • For resectable oligometastatic disease, surgical excision or stereotactic radiosurgery (SRS) should be considered whenever feasible, preferentially combined with adjuvant systemic therapies. [1]
  • Adjuvant radiotherapy shows benefits for lymph-node field control in patients at high risk of lymph-node field relapse after therapeutic lymphadenectomy but does not improve overall survival or metastasis-free survival and increases the risk of regional toxicity. [1]
  • Antibiotics, proton pump inhibitors (PPIs), and probiotics: A meta-analysis examined whether exposure to proton pump inhibitors (PPIs), antibiotics, or probiotics before or during immune checkpoint inhibitor therapy affected outcomes such as progression-free survival, overall survival, and objective response rate in patients with cancers treated with ICIs (including melanoma). [29]
  • systemic glucocorticoids: Observational evidence on systemic glucocorticoid use and melanoma risk is inconsistent. [38]
  • systemic medical treatment: Systemic medical treatment is indicated in the absence of surgical options for distant metastasis, but systemic medical treatments have had low response rates to date (systemic medical treatment). [3]
  • multimodality treatment: Multimodality treatment was reported as the approach for the majority of cases: 2990 of the total 3824 cases were treated with multimodality treatment. [32]
    cases treated only surgically 772 vs 3824 vs of total casescases treated with proton technique and SFUD 20 vs 3824 vs of total casescases treated with proton technique and IMRT 42 vs 3824 vs of total casescases treated with multimodality treatment 2990 vs 3824 vs of total cases
    Source quotes
    • “All 772 cases of total 3824 were treated only surgically.”
    • “All 62 cases of total 3824 were treated without surgery, 20 cases with proton technique and SFUD, and 42 cases with proton technique and IMRT.”
    • “All 62 cases of total 3824 were treated without surgery, 20 cases with proton technique and SFUD, and 42 cases with proton technique and IMRT.”
    • “The other 2990 cases of total 3824 were treated with multimodality treatment.”
Staging & risk5 points

Key figures

Survival & outcomes
OutcomeValue95% CI
median correlation coefficient (HFUS vs histopathology)0.94—
Source quotes
  • “Correlation coefficients between HFUS and histopathology ranged from 0.417 to 0.997 (median: 0.94, mean: 0.89 and SD: 0.13; Figure 2).”
  • Sources state that staging of cutaneous melanoma is based on the AJCC system. [1][8][3]3 sources
  • The AJCC 7th Edition (2009) included staging revisions and identified primary tumour mitotic rate as an important independent prognostic indicator; more generally, factors such as Breslow depth, mitotic rate and presence of tumour ulceration significantly influence patient survival and are important for staging. [2][37]
  • Guidelines recommend CT and/or MRI for patients with high-risk melanoma and brain imaging for those with stage IV disease. [1][2]
  • Sentinel lymph node dissection is routinely offered as a staging procedure in patients with tumours more than 1mm in thickness, although there is as yet no clear survival benefit for this approach. [8]
  • Correlation coefficients between high-frequency ultrasound (HFUS) and histopathology for tumour depth measurements ranged from 0.417 to 0.997 with a median of 0.94 across studies in the meta-analysis; lower-frequency ultrasound probes (10–20 MHz) were reported to be less accurate for tumour thickness assessment, with cumulative mean correlation coefficients of 0.87 (10–20 MHz), 0.94 (20–25 MHz), and 0.98 (≥70 MHz). [37]
Prognosis13 points

Key figures

Survival & outcomes
OutcomeValue95% CI
proportion of skin cancer mortality caused by cutaneous melanoma90%—
1-year survival52%—
local_recurrence_rate25.9%—
distant_metastasis_rate38.8%—
crude_overall_survival48%—
5-year_survival_estimate74%—
Prognostic factors
FactorEffectHR (95% CI)p
stage-matched PAM vs non-PAM▼ better0.85 (0.73–1)—
Source quotes
  • “Cutaneous melanoma (CM) is potentially the most dangerous form of skin tumour and causes 90% of skin cancer mortality.”
  • “Survival rates decline sharply over time—from 52% at one year to 25% at two years and just 13% at three years (2, 3).”
  • “Local recurrence occurred in 25.9% of cases and distant metastasis in 38.8%.”
  • “Local recurrence occurred in 25.9% of cases and distant metastasis in 38.8.”
  • “Crude overall survival was approximately 48%, whereas Kaplan-Meier analysis demonstrated an estimated 5-year survival of 74%.”
  • “Stage-matched evidence yielded a borderline-significant pooled HR of 0.85 (95% CI 0.73-1.00; I²=0%) favouring PAM.”
  • Cutaneous melanoma causes 90% of skin cancer mortality and accounts for the majority of skin cancer–related deaths. [8][39]
  • In a lip melanoma review, local recurrence occurred in 25.9% of cases, distant metastasis occurred in 38.8% of cases, crude overall survival was approximately 48%, and Kaplan–Meier analysis demonstrated an estimated 5-year survival of 74%. [21]
  • Metastatic uveal melanoma has a poor prognosis with a reported median survival of approximately 12 months and rapidly declining survival rates over 1–3 years. [33]
  • Sentinel lymph node dissection has, as yet, shown no resultant survival benefit. [3]
  • Although interferon-alpha increases relapse-free survival as adjuvant therapy, it lacks a clear survival benefit and toxicity limits its use in practice. [3]
  • The meta-analysis concluded that PAM does not independently worsen overall survival (OS) or melanoma-specific survival (MSS) when stage is adequately controlled. [22]
  • The pooled analysis found that neither antepartum (HR 1.13, 95% CI 0.19-6.70; I²=65.6%) nor postpartum PAM (HR 1.14, 95% CI 0.39-3.38; I²=54.8%) showed a significant overall survival difference. [22]
  • Stage-matched evidence produced a borderline-significant pooled hazard ratio of 0.85 (95% CI 0.73-1.00) favouring PAM. [22]
  • Treatment is usually curative following early detection of disease. [39]
  • Guidelines indicate that treatment decisions, such as excision margins, depend on melanoma depth. [2]
  • One-third of patients with resected metastasis may become long-term survivors. [1]
  • Ulcerated melanomas are more likely to undergo sentinel lymph node biopsy and are described as more likely to benefit from adjuvant therapies, which has implications for prognosis and treatment opportunity. [26]
  • In a systematic review and meta-analysis of time-of-day ICI administration, the primary outcomes were overall survival and progression-free survival. [16]
Safety & interactions12 points
  • Among 198,514 patients included in a scoping review of cutaneous immune-related adverse events, 24,814 patients (12.5%) experienced at least one cirAE; in the cirAEs literature, the majority of cirAE patients experienced grades 1–2 and 2.6% of cirAE patients reported grades 3–4; lower baseline neutrophil-to-lymphocyte ratio (low NLR) has been reported as a biomarker associated with increased risk of cutaneous immune-related adverse events. [19]
  • Health maintenance recommendations for patients with inflammatory bowel disease include screening for melanoma and non-melanoma skin cancer. [40]
  • There are insufficient data to comment on the risk of melanoma associated with fertility drug use. [41]
  • Guidelines summarize the management of dermatologic toxicities related to novel targeted agents and immunotherapies for patients with advanced melanoma. [39]
  • Interferon-α adjuvant treatment is associated with significant toxicity. [8]
  • In systematic reviews of DMARD safety, increased nonmelanoma skin cancer (NMSC) was noted in patients with rheumatoid arthritis using DMARDs compared with the general population, without a link to a specific DMARD. [42]
  • Colitis is reported as one of the most prevalent clinical manifestations of immune checkpoint inhibitor–related adverse events. [43]
  • Combination therapy with CTLA-4 plus PD-1 inhibitors was reported to be more likely to cause gastrointestinal adverse events and to increase immune-related adverse events compared with single agents; CTLA-4 inhibitors were associated with a higher risk and more severe incidence of immune-related adverse events compared to other immune checkpoint inhibitors in the reviewed analyses. [6]
  • A pooled analysis of clinical trials of immune checkpoint inhibitors estimated the overall pooled incidence of neurological adverse events as 1.78*10–3% (95%CI 1.06*10–3%–2.78*10–3%); in the subgroup of trials that included melanoma patients (n = 5 trials), the pooled incidence of neurological adverse events was reported as 1.16*10–3% (95%CI 0.22*10–3%–2.71*10–3%). [35]
  • In randomized trials of cancer vaccine therapies for malignant melanoma, adverse events did not increase significantly compared with controls in pooled analyses. [34]
  • Combined intrathecal and intravenous nivolumab in melanoma leptomeningeal disease was reported as feasible with manageable toxicity. [11]
  • Systematic reviews of observational studies found inconsistent results for an association between systemic glucocorticoid use and melanoma risk; observational studies assessing systemic glucocorticoids and site-specific cancers face significant methodologic issues that may compromise the validity of their findings. [38]
What we don't know yet19 points
  • Because POT1 germline pathogenic variants are rare and data are limited, the overall lifetime cancer risks for POT1-TPDS carriers are unclear. [44]
  • No recommendation could be made for or against the use of neoadjuvant therapy in cutaneous melanoma. [9]
  • No recommendation could be made for or against specific systemic therapy for uveal melanoma. [9]
  • Ano-uro-genital (AUG) mucosal melanomas are rare, are associated with poor outcomes, and have limited evidence to guide management. [45]
  • The value of adjuvant radiation for patients at high risk of nodal relapse remains controversial. [7]
  • There is not yet clear evidence of a survival benefit from offering routine sentinel lymph node dissection as a staging procedure for patients with tumours more than 1 mm in thickness. [8]
  • The relationship between alopecia areata and skin cancer, including melanoma, remains uncertain. [13]
  • Phase-3 trials are underway to evaluate whether the phase 2b signal for mRNA-4157/V940 plus pembrolizumab is confirmed. [28]
  • For pucotenlimab, the combined effects and sources of heterogeneity of objective response rate, progression-free survival, and overall survival across different tumor types have not been clarified, and there is a reported lack of direct or indirect comparative evidence among different combination chemotherapy regimens. [10]
  • Prospective validation of artificial intelligence diagnostic tools for skin cancer in real-world clinical workflows remains limited. [30]
  • Genomic differences between primary and metastatic melanoma underscore the value of metastatic tumor biopsies for informing molecularly guided treatment decisions. [4]
  • New treatment targets are urgently needed because melanoma can stop responding to existing immunotherapies and targeted therapies. [4]
  • More evidence is required about the potential benefits, harms, and costs of organised skin cancer screening. [18]
  • Current evidence on beta-blockers is insufficient to recommend them for melanoma treatment, and further research focusing on pan-selective beta-blockers has been suggested. [36]
  • Future registries must adopt standardised PAM definitions and ensure complete staging to yield reliable survival estimates. [22]
  • Standardised LMD-specific outcomes and controlled comparative trials are needed to define best practice. [11]
  • Proposed hypotheses on mechanisms linking vitiligo and skin cancer risk may involve both immune-mediated and nonimmune-mediated pathways. [14]
  • Observational studies assessing systemic glucocorticoid use and site-specific cancer risk have methodologic limitations; robust study designs and analytic approaches are needed to generate unbiased estimates of drugs' effects on cancer incidence. [38]
  • Existing observational studies investigating the association between type 2 diabetes mellitus and cancer have important limitations and have not yielded definitive, consistent conclusions. [27]

Sources

Every statement above is drawn from these reviewed sources. This page reports what they describe. Sources last checked June 19, 2026.

  1. GuidelineSEOM-GEM clinical guidelines for cutaneous melanoma (2023) · 2024
  2. GuidelineHead and neck melanoma (excluding ocular melanoma): United Kingdom National Multidisciplinary Guidelines · 2016
  3. GuidelineDiagnosis and treatment of melanoma: European consensus-based interdisciplinary guideline · 2010
  4. Systematic reviewGenomics of Primary and Metastatic Cutaneous Melanoma: A Systematic Review and Meta-Analysis · 2026
  5. Meta-analysisGenetic causality linking skin microbiota to skin cancer: Mendelian randomization study and meta-analysis · 2025
  6. Meta-analysisUmbrella Systematic Review of the Efficacy and Safety of PD-1 Inhibitors Combined with CTLA-4 Inhibitors in the Treatment of Melanoma · 2026
  7. GuidelineMelanoma, version 4.2014 · 2014
  8. GuidelineDiagnosis and treatment of melanoma. European consensus-based interdisciplinary guideline--Update 2012 · 2012
  9. GuidelineSystemic Therapy for Melanoma: ASCO Guideline · 2020
  10. Meta-analysisIntegration Analysis of Bayesian and Machine Learning for Heterogeneity, Biomarkers, and Optimal Combination Regimens of Pucotenlimab in Solid Tumors · 2026
  11. Systematic reviewUpdate on the management of leptomeningeal disease in solid organ malignancy: Systemic, intrathecal and novel therapies · 2026
  12. Meta-analysisDermatologic Features of Endocrine Tumor Syndromes-Systematic Review and Meta-Analysis · 2026
  13. Systematic reviewSkin cancer risk in alopecia areata: a systematic review and meta-analysis · 2026
  14. Meta-analysisThe Risk of Keratinocyte Cancer in Vitiligo and the Potential Mechanisms Involved · 2024
  15. Meta-analysisATP5B Expression as a Prognostic Biomarker in Solid Tumors: A Systematic Review and Meta-Analysis · 2026
  16. Meta-analysisTime-of-Day Immunotherapy Administration and Outcomes in Advanced Cancers: A Systematic Review and Meta-Analysis · 2026
  17. Meta-analysisThe Safety and Efficacy of Anti-LAG-3 for Patients with Melanoma: A Systematic Review and Meta-analysis Study · 2026
  18. Systematic reviewA systematic review of microsimulation models for skin cancer · 2025
  19. Systematic reviewRisk factors for cutaneous immune-related adverse events: a systematic scoping review · 2026
  20. Systematic reviewMalignant Melanoma Misdiagnosis in the Diabetic Foot. What Can We Learn From the Published Literature? · 2026
  21. Systematic reviewLip Melanoma: A Systematic Review of the Literature · 2026
  22. Meta-analysisThe prognostic impact of pregnancy-associated melanoma on overall and melanoma-specific survival: A systematic review and meta-analysis · 2026
  23. GuidelineNon-melanoma Skin Cancer in Canada Chapter 1: Introduction to the Guidelines · 2015
  24. GuidelineGuideline on the management of melanoma · 2004
  25. Meta-analysisSurgical margin assessment and prognostic impact in sinonasal cancers: a systematic review and meta-analysis · 2025
  26. Meta-analysisImpact of the COVID pandemic on melanoma thickness and ulceration: a meta-analysis · 2025
  27. Meta-analysisType 2 diabetes mellitus and cancer: A systematic review and meta-analysis of Mendelian randomization studies · 2026
  28. Systematic reviewNanoparticle-mediated mRNA delivery for cancer, autoimmunity, and genetic diseases: a rapid review · 2026
  29. Meta-analysisUnraveling gut microbiome interferences in cancer immunotherapy: a meta-analysis of diverse drug effects · 2025
  30. Systematic reviewEvaluating the Performance of Artificial Intelligence in Accurately Detecting Skin Cancer: An Umbrella Review of Systematic Reviews and Meta-analyses · 2026
  31. Systematic reviewA comprehensive review of deep learning applications in the segmentation and classification of skin cancer · 2026
  32. Systematic reviewNasal Cavity and Paranasal Sinus Cancer: Diagnosis and Treatment · 2024
  33. Systematic reviewComparative efficacy of therapeutic modalities for metastatic uveal melanoma: a systemic review and network meta-analysis · 2026
  34. Meta-analysisEfficacy and safety of cancer vaccine therapy in malignant melanoma: a systematic review · 2025
  35. Meta-analysisThe neurological adverse events of immune check point inhibitors in the treatment of cancer · 2026
  36. Meta-analysisBeta-Blockers and Cutaneous Melanoma Outcomes: A Systematic Review and Random-Effects Meta-Analysis · 2025
  37. Meta-analysisHigh-frequency ultrasound accuracy in preoperative cutaneous melanoma assessment: A meta-analysis · 2025
  38. Systematic reviewSystemic Glucocorticoid Use and Risk of Site-Specific Cancers: A Methodologic Systematic Review of Observational Studies · 2026
  39. GuidelineGuidelines of care for the management of primary cutaneous melanoma · 2019
  40. GuidelineACG Clinical Guideline Update: Preventive Care in Inflammatory Bowel Disease · 2025
  41. GuidelineFertility drugs and cancer: a guideline · 2024
  42. Systematic reviewSafety of synthetic and biological DMARDs: a systematic literature review informing the 2025 update of the EULAR recommendations for the management of rheumatoid arthritis · 2026
  43. Systematic reviewResearch landscape, thematic evolution, and translational insights of immune checkpoint inhibitor-induced colitis: a bibliometric analysis (2006-2025) · 2026
  44. GuidelineUK clinical practice guidelines for the management of patients with constitutional POT1 pathogenic variants · 2025
  45. GuidelineAno-uro-genital mucosal melanoma UK national guidelines · 2020

What supports this page

The kinds of sources behind this page, strongest at the top. Faint rungs show what is not here yet.

Guideline
46
Meta-analysis
138
Systematic review
56
Randomized trial
1
Clinical trial
13
Observational
3
Case report
98
Review
1095
Preclinical
0
Other
11

Living document — last change June 19, 2026: Cancer page updated. 3 recent updates logged.

Pooled evidence across studies

PubMed
  • ASCVD incidence: HR 1.56 (0.91–2.8 across studies) · (regimen unspecified)
    3 studies · 33% agree · heterogeneous40445187

Numbers pooled deterministically across 7 published studies that passed our figure-accuracy checks — a quick synthesis, not a formal meta-analysis. Updated 6/27/2026.

What recent studies report in Melanoma

These are reviewed studies whose abstracts concern Melanoma. Each describes only what that study reported. This is not a claim by OncoForge that any compound helps or harms Melanoma. Most are early lab, animal, or small human studies, and findings often conflict.

40 studies4 human1 animal⚠ Conflicting evidenceMechanism (16)Supportive care (1)

Tracking 40 published studies of Melanoma: 4 in humans, 1 in animals, 35 reviews/other.

Reported direction across studies: 13 positive, 9 mixed, 1 negative, 17 inconclusive.

Findings conflict — both supportive and negative/mixed results exist (see below). Human evidence is limited.

These counts summarize what the studies reported; they are not a measure of whether anything works for Melanoma.

Animal studyReported positivePreclinical onlyTier 2 · animal

A humanized anaplastic lymphoma kinase (ALK)-directed antibody-drug conjugate with pyrrolobenzodiazepine payload demonstrates efficacy in ALK-expressing cancers

Nature communications · Aug 2025 · xenograft antitumor assays

neuroblastomarhabdomyosarcomacolorectal carcinomamelanomaovarian carcinomabreast carcinoma

This study tested a humanized antibody-drug conjugate called CDX0239-PBD in ALK-expressing cancer models. In cell lines, it was taken up by ALK-positive neuroblastoma cells and killed them in a way that depended on surface ALK expression. In mouse xenograft models, it produced strong antitumor activity and complete responses were maintained in several ALK-expressing cancers.

Key findings
  • ALK RNA, protein, and tumor cell surface expression was elevated in multiple pediatric and adult malignancies with minimal expression in childhood normal tissues.
  • CDX0239-PBD was internalized in ALK-expressing neuroblastoma cell lines with cell surface expression-dependent cytotoxicity.
  • CDX0239-PBD exhibited potent antitumor efficacy including maintained complete responses in ALK-expressing patient and cell line-derived neuroblastoma, fusion-positive rhabdomyosarcoma, and colorectal carcinoma xenograft models.
Limitations: Preclinical study only; no human treatment data are reported in the abstract.; Efficacy was shown in cell lines and xenograft mouse models, which may not predict clinical benefit.; No quantitative effect sizes, dosing details, or toxicity results are provided in the abstract..

The abstract describes a preclinical anticancer antibody-drug conjugate targeting ALK-expressing tumors.

AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed · Full text

Human · observationalSupportive careMixed resultsModerate evidenceTier 3 · early humann = 267586

Risk of atherosclerotic cardiovascular disease after cancer diagnosis: findings from 3 prospective cohort studies

Journal of the National Cancer Institute · Aug 2025 · prospective cohort study

Supportive carecervical cancerHodgkin lymphomaprostate cancerbreast cancercolorectal cancerlung cancerendometrial canceroral cavity and pharynx cancerkidney cancerovarian cancersarcomamelanomaleukemia

Researchers followed participants in three large prospective cohorts for up to 36 years to examine whether a cancer diagnosis was associated with later atherosclerotic cardiovascular disease (ASCVD). They documented 4,334 new ASCVD events among 49,603 incident cancer cases and found that cervical cancer and Hodgkin lymphoma were associated with higher ASCVD risk, prostate cancer with slightly lower risk, and that ASCVD risk trajectories over time varied by cancer type (for example, breast cancer survivors had lower ASCVD risk for the first 7.5 years, then risk increased).

Reported effects: new-onset ASCVD events among incident cancer cases 4334, n=49603 · cervical cancer HR 1.56 [1.06–2.29] · +6 more

Key findings
  • During up to 36 years of follow-up, 4,334 new-onset ASCVD events among 49,603 incident cancer cases were documented.
  • Cervical cancer was associated with increased ASCVD incidence (HR = 1.56, 95% CI = 1.06 to 2.29).
  • Hodgkin lymphoma was associated with increased ASCVD incidence (HR = 2.80, 95% CI = 1.89 to 4.15).
  • Prostate cancer was associated with lower ASCVD incidence (HR = 0.91, 95% CI = 0.85 to 0.97).
  • Breast cancer survivors experienced lower ASCVD risk during the first 7.5 years after diagnosis, but risk gradually increased afterward (Pnonlinearity = .01).
  • ASCVD risk increased over time among patients with cancers of the colorectum (P = .003), lung (P = .002), and endometrium (P = .04).
  • No statistically significant association with ASCVD risk was observed for cancers of the oral cavity and pharynx, kidney, or ovary; sarcoma; melanoma; or leukemia.
Limitations: Observational cohort design cannot establish causality.; Potential for residual confounding despite multivariable adjustment.; Cohorts consist of nurses and health professionals, which may limit generalizability to other populations.; Abstract does not report details on cancer stage or treatments, which could influence ASCVD risk..

AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed · Full text

ReviewInconclusivePreclinical onlyTier 4 · clinical

Metabolic reprogramming in melanoma therapy

Cell death discovery · Jul 2025

melanoma

This is a review summarizing recent studies on how metabolic reprogramming supports melanoma growth, proliferation, metastasis, and resistance to therapy. It discusses metabolic pathways involved in melanoma progression and considers targeting these pathways alone or combined with existing therapeutic inhibitors as a potential strategy.

Studied with: established therapeutic inhibitors.

Key findings
  • Melanoma exhibits metabolic reprogramming that supports energy production, biosynthesis, tumor progression, and therapy resistance.
  • The review summarizes recent studies elucidating metabolic pathways involved in melanoma progression, therapeutic response, and resistance.
  • The authors discuss potential of targeting metabolic pathways, alone or in combination with established therapeutic inhibitors, to block melanoma progression.
Limitations: Review article with no original experimental or clinical data reported.; Abstract does not state systematic-review methods or provide search strategy, so selection bias is possible.; Conclusions are narrative and may be speculative without new experimental validation presented in this paper..

AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed · Full text

ReviewReported positiveLimited evidenceTier 4 · clinical

Radiation Therapy for Metastatic Melanoma

Dermatologic clinics · Jul 2025 · narrative review

metastatic melanomabrain metastases

This narrative review summarizes how radiation therapy (RT) is being used in metastatic melanoma and how its role has evolved. The authors describe RT's value for local control, palliation, and management of brain metastases, and discuss emerging evidence of synergy between RT and immune checkpoint inhibitors, including the abscopal effect.

Studied with: immune checkpoint inhibitors.

Key findings
  • Metastatic melanoma is aggressive with a low 5-year survival rate of 27%.
  • Melanoma was historically considered radioresistant, but responses to radiation therapy have evolved, particularly when combined with systemic therapies such as immune checkpoint inhibitors.
  • Radiation therapy is now recognized for utility in local control, palliative care, and management of brain metastases in metastatic melanoma.
  • Emerging evidence indicates synergy between radiation therapy and immune checkpoint inhibitors, with mechanisms such as the abscopal effect under investigation.
Limitations: This is a review article and does not present original trial data.; Abstract provides no details on radiation doses, schedules, or specific clinical trial results.; Evidence for synergy with immune checkpoint inhibitors is described as emerging, indicating limited or early-stage data.; The abstract does not state this is a systematic review or meta-analysis, so the review methodology and comprehensiveness are unclear..

Discusses the clinical role of radiation therapy in metastatic melanoma and its integration with immune checkpoint inhibitors.

AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed

ReviewReported positiveLimited evidenceTier 3 · early human

Primary dermal melanoma

Clinics in dermatology · May 2025 · review

primary dermal melanomamelanomaskin neoplasms

This review summarizes primary dermal melanoma (PDM), a rare (<1%) melanoma subtype that occurs entirely in the dermis or subcutis and lacks connection to the epidermis. It emphasizes that PDM can histologically mimic cutaneous melanoma metastasis, explains that careful history, exam, and imaging are needed to exclude other primaries, and notes that PDM is associated with an unexpectedly favorable prognosis.

Reported effect: estimated incidence

Key findings
  • Primary dermal melanoma (PDM) is a rare subtype of melanoma with an estimated incidence of <1%.
  • PDM manifests entirely in the dermis or subcutis and histopathologically mimics cutaneous melanoma metastasis due to its lack of connection to the overlying epidermis.
  • A thorough history and examination, including imaging evaluation for metastatic disease, reveals no prior history or concurrent primary cutaneous or metastatic melanoma lesion.
  • Despite its histopathologic similarities to melanoma metastasis, PDM is associated with an unexpectedly favorable prognosis.
  • The review discusses the clinical and histopathologic features of PDM as a distinct subtype of melanoma, as well as the current approach to clinical staging and management.
Limitations: Narrative review rather than a systematic review or meta-analysis (no primary data reported in abstract).; PDM is rare (<1%), so the evidence base is likely limited by small numbers and case series.; Histopathologic similarity to metastatic melanoma may complicate diagnosis and classification in published reports..

AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed

ReviewInconclusiveLimited evidenceTier 4 · clinical

Current Treatment of Uveal Melanoma

Cancers · Apr 2025

uveal melanoma

This is a review article titled "Current Treatment of Uveal Melanoma" that discusses treatments for uveal melanoma. The provided abstract text is incomplete and does not report specific interventions, results, or conclusions.

Limitations: Provided abstract is incomplete/truncated and contains no detailed results.; Review article — no original experimental or clinical trial data reported in the abstract.; No specific treatments, doses, outcomes, or quantitative results are stated in the provided text.; Unable to assess study design, population, or funding from the abstract..

AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed · Full text

ReviewInconclusiveLimited evidenceTier 4 · clinical

Melanoma in pregnancy

Seminars in perinatology · Mar 2025

cutaneous melanomamelanoma

This narrative review summarizes published literature on cutaneous melanoma diagnosed during pregnancy. The authors report that pregnancy does not appear to worsen maternal melanoma outcomes and, except for rare placental or fetal metastases, melanoma usually does not cause major obstetric or fetal complications. They note that localized melanoma is managed according to general population guidelines, while advanced melanoma in pregnancy is challenging because of limited research and lack of unified management recommendations.

Key findings
  • Cutaneous melanoma is the most common malignancy in women of childbearing age and accounts for nearly one-third of malignancies diagnosed during gestation.
  • Based on available literature, pregnancy does not seem to worsen maternal outcomes from melanoma.
  • Aside from placental and fetal metastases, melanoma does not seem to cause serious obstetric or fetal complications.
  • Treatment of localized melanoma during pregnancy follows guidelines for the general population.
  • Advanced melanoma in pregnancy poses unique challenges due to lack of unifying research and management recommendations.
  • The review highlights diagnostic clinical pearls and multidisciplinary management considerations for melanoma in the child-bearing population.
Limitations: Narrative review with no primary data reported in this article.; Abstract states pathophysiology during pregnancy is not well understood, indicating knowledge gaps.; Authors note a lack of unifying research and management recommendations for advanced melanoma in pregnancy, implying limited high-quality evidence..

AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed

Case reportInconclusiveLimited evidenceTier 3 · early humann = 1

Incidental Cutaneous Melanoma

Journal of Brown hospital medicine · Jul 2024

cutaneous melanoma

This single-patient case report describes a young man who was admitted with sepsis and cellulitis and was incidentally found to have invasive cutaneous melanoma. The authors emphasize that recognizing melanoma is important to ensure timely diagnosis and treatment.

Key findings
  • A young man admitted to the hospital with sepsis and cellulitis was incidentally found to have invasive cutaneous melanoma.
  • The authors state that recognition of melanoma is important to ensure timely diagnosis and treatment.
Limitations: Single case report (n=1) limits generalizability; Abstract provides no systematic data, outcomes, or follow-up information; No control or comparison group; No details on management, staging, or prognosis in the abstract.

AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed · Full text

ReviewInconclusiveLimited evidenceTier 4 · clinical

Anorectal melanoma

Journal of surgical oncology · Sep 2023

anorectal melanomamucosal melanomacutaneous melanoma

This is a narrative review about anorectal (mucosal) melanoma, an aggressive subtype with a poor prognosis. The authors summarize differences in pathogenesis between mucosal and cutaneous melanoma, discuss new staging concepts for mucosal melanoma, and provide updates on surgical management. They also review current data on adjuvant radiation and systemic therapy and note that the optimal treatment paradigm is evolving.

Key findings
  • Anorectal melanoma is an aggressive mucosal melanoma subtype with a poor prognosis.
  • The optimal treatment paradigm for management of anorectal melanoma is evolving.
  • The review highlights differences in the pathogenesis of mucosal versus cutaneous melanoma.
  • The review discusses new concepts of staging for mucosal melanoma.
  • Updates to surgical management of anorectal melanoma are presented.
  • Current data for adjuvant radiation and systemic therapy in this patient population are reviewed.
Limitations: Review article — no new primary patient-level data or experiments reported.; Abstract provides no quantitative results, methods, or details of search methodology.; Because this is a review, conclusions depend on the underlying studies and are not original findings..

AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed

OtherReported positivePreclinical onlyTier 1 · lab

Nanosonosensitizers-engineered injectable thermogel for augmented chemo-sonodynamic therapy of melanoma and infected wound healing

Materials today. Bio · Mar 2023

melanoma

The authors engineered an injectable thermosensitive chitosan hydrogel (CuO2-BSO@Gel) containing CuO2 nanodots and the GSH-depleting agent BSO. In the reported work the CuO2 nanodots provided H2O2 for Fenton-like chemodynamic reactions and acted as sonosensitizers (bandgap 2.29 eV), while BSO depleted glutathione to amplify oxidative stress and trigger ferroptosis. The hydrogel formulation also promoted proliferation of normal skin cells and accelerated healing of bacteria-infected wounds, with reported antibacterial activity and enhanced angiogenesis.

Reported effect: bandgap 2.29

Studied with: chemo-sonodynamic therapy, chemodynamic therapy, GSH depletion (BSO).

Key findings
  • An injectable thermosensitive chitosan hydrogel (CuO2-BSO@Gel) was constructed by integrating CuO2 nanodots and BSO with a thermoresponsive hydrogel.
  • CuO2 nanodots can self-supply H2O2 under acidic tumor microenvironment and, via the Fenton catalytic activity of Cu2+, achieve enhanced chemodynamic therapy (CDT).
  • CuO2 nanodots have a narrow bandgap (2.29 eV) and were reported to be efficient sonosensitizers; the quantum yield of singlet oxygen (1O2) could be boosted by O2 generation during Fenton-like reactions.
  • Loaded BSO depletes intracellular glutathione (GSH), amplifying oxidative stress induced by SDT and CDT and leading to ferroptosis.
  • The multifunctional hydrogel promoted proliferation of normal skin cells and accelerated bacteria-infected wound healing through chemo-sonodynamic antibacterial activity and enhanced angiogenesis.
  • The authors report desirable biocompatibility and bioactivity for the engineered thermogel.
Limitations: Abstract does not state the experimental model(s) used (in vitro versus animal), so translational relevance is unclear from the abstract alone.; No sample sizes, quantitative efficacy metrics (for biological outcomes), or statistical results are reported in the abstract.; No information on safety, systemic toxicity, or long-term outcomes is provided in the abstract.; Findings are preclinical (no human data reported in the abstract).; Abstract does not report detailed dosing, treatment schedules, or comparator controls..

AI summary of the abstract, human-reviewed · Jul 2026. Describes what this study reported, not medical advice. View on PubMed · Full text

OtherMechanismReported positiveLimited evidenceTier 3 · early humann = 10

Impact of early detection on cancer curability: A modified Delphi panel study

PloS one · Dec 2022 · RAND/UCLA modified Delphi panel

stomachesophaguslungurothelial tractmelanomaovarysarcomabladdercervixbreastcolon/rectumkidneyuterusanushead and neckliver/intrahepatic bile ductgallbladderpancreasprostatethyroid

Ten practicing oncologists used a RAND/UCLA modified Delphi panel to rate 20 solid tumor types for potential clinical benefit from a hypothetical annual multi-cancer screening blood test. Cancers judged to progress quickly but be more curable at early stages (e.g., stomach, esophagus, lung, melanoma, ovary, sarcoma, bladder, cervix, breast, colon/rectum, kidney, uterus, anus, head and neck) were rated most likely to benefit. Cancers judged to progress quickly but with lower early-stage cure rates (liver/intrahepatic bile duct, gallbladder, pancreas) were rated as having medium likelihood of benefit. Prostate and thyroid, judged to progress more slowly and be curable regardless of stage, were rated as having limited likelihood of benefit.

Key findings
  • Expert ratings identified a group of cancers estimated most likely to benefit from a hypothetical annual multi-cancer screening blood test: stomach, esophagus, lung, urothelial tract, melanoma, ovary, sarcoma, bladder, cervix, breast, colon/rectum, kidney, uterus, anus, head and neck.
  • Cancers rated as progressing quickly but with comparatively lower cure rates in earlier stages (liver/intrahepatic bile duct, gallbladder, pancreas) were estimated to have medium likelihood of benefit.
  • Cancers rated as progressing more slowly and having higher curability regardless of stage (prostate, thyroid) were estimated to have limited likelihood of benefit.
  • The panel concluded most solid tumors have a likelihood of benefit from early detection and that early-stage detection was believed to be beneficial even among difficult-to-treat cancers (e.g., pancreas, liver/intrahepatic bile duct, gallbladder).
  • The 20 solid tumors evaluated represent >40 AJCC-identified cancer types and 80% of total cancer incidence (as stated in abstract).
Limitations: Small expert panel (10 oncologists) — results reflect opinions of a limited number of experts.; Delphi consensus of expert opinion rather than empirical patient-level outcomes or clinical trial data.; Assessment based on a hypothetical annual multi-cancer screening blood test rather than an evaluated diagnostic with measured performance.; No patient data, clinical endpoints, or real-world screening test performance reported in this study..

Expert consensus assessing which solid tumor types might gain clinical benefit from earlier detection via a hypothetical multi-cancer blood screening test.

AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed · Full text

Human · observationalMechanismReported positiveLimited evidenceTier 3 · early humann = 10000

The BRCAness Landscape of Cancer

Cells · Dec 2022 · pan-cancer computational/genomic characterization across tumor cohorts

breast cancerovarian canceradrenocortical carcinomabladder urothelial carcinomabrain lower grade gliomacolon adenocarcinomaesophageal carcinomahead and neck squamous carcinomakidney chromophobekidney renal clear cell carcinomakidney renal papillary cell carcinomaliver hepatocellular carcinomalung adenocarcinomalung squamous cell carcinomamesotheliomarectum adenocarcinomapancreatic adenocarcinomaprostate adenocarcinomasarcomaskin cutaneous melanomastomach adenocarcinomauterine carcinosarcomauterine corpus endometrial carcinoma

The authors performed a computational characterization of 40 BRCAness-related genes across 33 cancer types using over 10,000 cancer cases, assessing mutations, deletions, promoter hypermethylation, gene expression, and clinical correlations. Using BRCA1/BRCA2-mutated breast and ovarian cancers as controls, they found BRCAness features widely present across multiple cancer types and identified 21 cancer types as potential targets for PARP inhibitor therapy.

Reported effects: BRCAness-related genes analyzed 40 · cancer_types_analyzed 33 · +2 more

Key findings
  • Comprehensively characterized 40 BRCAness-related genes across 33 cancer types in over 10,000 cancer cases, examining pathogenic variation, homozygotic deletion, promoter hypermethylation, gene expression, and clinical correlation.
  • Used BRCA1/BRCA2-mutated breast and ovarian cancer as controls for BRCAness features.
  • Observed that BRCAness is widely present in multiple cancer types beyond breast and ovarian cancer.
  • Identified 21 cancer types as potential targets for PARP inhibitor (PARPi) therapy based on the summed BRCAness features in each cancer type.
Limitations: Observational computational analysis only; no experimental or functional validation reported in this abstract.; The study does not report testing PARP inhibitors directly in these cancers or provide clinical efficacy data.; BRCAness features are used as surrogate molecular markers for PARPi sensitivity; functional sensitivity was not demonstrated.; Sample size is reported only as 'over 10,000' cases in the abstract (exact counts by cancer type not provided)..

AI summary of the abstract, human-reviewed · Jul 2026. Describes what this study reported, not medical advice. View on PubMed · Full text

Browse all studies mentioning Melanoma →

Study mix

40 published studies by what they were done in. Lab and animal findings often do not carry over to people.

4 Human1 Animal35 Review/other
Reported directionReported positive13Mixed results9Reported negative1Inconclusive17

What the research shows for Melanoma

A plain-language summary of the reviewed studies OncoForge tracks for Melanoma. It reports what those studies described, not a claim that any compound or therapy helps or harms Melanoma. Most of this evidence is early, and findings often conflict.

  • A review (PMID 15563313) describes vasculogenic mimicry in aggressive melanoma, where tumor cells form fluid-conducting, vascular-like channels observed in tumor specimens and experimental models.
  • The review distinguishes two morphological types of vasculogenic mimicry described in melanoma: tubular channels and patterned-matrix channels.
  • The review reports that patterned-matrix channels contain extracellular matrix proteins and can connect with established blood vessels.
  • The review characterizes the overall evidence as limited and inconclusive regarding the clinical significance or therapeutic implications of vasculogenic mimicry in melanoma.
  • A separate preclinical study (PMID 40813394) tested an antibody–drug conjugate (CDX0239‑PBD) in ALK‑expressing cancer cell lines and mouse xenografts (neuroblastoma, rhabdomyosarcoma, colorectal carcinoma) and did not report results for melanoma.

Supportive & alternative options discussed

  • Hyperthermia (heat): Also discussed as a supportive or adjunctive option in melanoma care by some sources; this was not examined in the studies summarized here.
  • Photodynamic therapy (PDT): Also discussed as a local therapy for certain skin lesions in melanoma management; this was not addressed by the studies summarized here.
  • Ketogenic / metabolic therapy: Also discussed by some patients and clinicians as a dietary approach adjunctive to cancer care; this was not examined in the studies summarized here.
  • Exercise / prehabilitation: Also discussed as supportive care to improve general health and quality of life for people with melanoma; this was not studied in the reports summarized here.
  • Mind–body (MBSR / CBT): Also discussed as supportive care to help with stress, coping, and quality of life in melanoma; this was not examined in the studies summarized here.
  • Acupuncture: Also discussed as a supportive option for symptom management in some patients with melanoma; this was not addressed in the studies summarized here.

What we don’t know yet

  • Whether vasculogenic mimicry affects clinical outcomes (prognosis, metastasis, or treatment resistance) in melanoma patients is not established by these reports.
  • There is no evidence from these studies that targeting vasculogenic mimicry improves patient outcomes; therapeutic strategies and clinical trial data are lacking.
  • How common vasculogenic mimicry is across melanoma subtypes and stages, and which biomarkers reliably detect it in patients, remain unclear.
  • Mechanistic pathways driving vasculogenic mimicry in human melanoma are not fully defined in the summarized literature.
  • Optimal methods to measure or image these channels in living patients, and the safety/long-term effects of intervening on them, are not addressed.
These reports are primarily descriptive and preclinical or limited reviews; they do not establish clinical relevance or support specific clinical interventions in melanoma.

Clinical trials in Melanoma

14 ongoing · 25 completed · tracked from ClinicalTrials.gov. Recruiting is not the same as proven, and completed is not the same as positive — read the results. Not a recommendation.

Completed
8 stopped (terminated / withdrawn / suspended)

Search all trials on ClinicalTrials.gov →

Getting care & support

Nonprofit / Gov

Practical, vetted help for Melanoma — advocacy, paying for treatment, second opinions, and caregivers.

If you’re struggling emotionally, you don’t have to wait.

Advocacy & community

No dedicated organization for this specific cancer is curated yet — these general organizations can help in the meantime.

Financial help

  • PAN Foundation ↗ — Copay assistance funds by diagnosis (funds open and close as money allows). · status changes often — check the fund’s site
  • HealthWell Foundation ↗ — Copay and premium assistance funds by disease. · status changes often — check the fund’s site
  • CancerCare — financial assistance ↗ — Limited grants plus free financial counseling. · status changes often — check the fund’s site
  • Family Reach ↗ — Help with everyday living costs (rent, transport, food) during treatment. · status changes often — check the fund’s site
  • NeedyMeds ↗ — Searchable directory of drug patient-assistance and discount programs. · status changes often — check the fund’s site
What you’ll typically need to apply
  • Your diagnosis and, if you have it, the specific drug/treatment name (from your care team).
  • Insurance details — your member ID card, or a note that you're uninsured (some funds require active insurance, some don't).
  • Proof of income and household size (recent pay stubs, a tax return, or a benefits letter) — most funds are income-based.
  • Your prescriber's contact information; some programs need the clinic to submit part of the application.
  • Apply early and re-check: funds open and close as money is available, so a closed fund may reopen.

General guidance — each program sets its own eligibility. Confirm requirements on the program’s site.

Second opinions

Caregiver support

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