ReviewMechanismInconclusiveLimited evidenceTier 4 · clinical
Expert review of anticancer therapy · Sep 2025 · narrative review
large cell neuroendocrine carcinoma of the lung
This narrative review summarizes current knowledge about large cell neuroendocrine carcinoma (LCNEC) of the lung, focusing on diagnostic criteria, molecular alterations, the tumor microenvironment including immune components, and ongoing clinical trials including immuno-oncology. The authors emphasize that LCNEC is a heterogeneous disease with distinct developmental trajectories that complicate diagnosis and clinical decision-making. They suggest this heterogeneity may provide a rationale for personalized targeted approaches or immunotherapy in patient subsets, but conclude that further studies using a holistic framework are needed.
Key findings
- LCNEC of the lung is described as a high-grade non-small cell carcinoma with neuroendocrine morphology and neuroendocrine markers.
- Diagnosis and therapeutic decision-making are challenging, likely because LCNEC comprises a heterogeneous mix of genetic and epigenetic alterations intertwined with the host microenvironment.
- The review structures LCNEC knowledge across three outlooks: (i) diagnostic criteria and molecular alterations; (ii) microenvironmental changes, including the immune system; and (iii) available clinical trials, including immune-oncology studies.
- Different developmental trajectories of LCNEC may explain diagnostic and treatment difficulties and may offer a rationale for personalized targeted therapies or immunotherapy in subsets of patients.
- The authors call for future studies to frame LCNEC within a broader, holistic context among lung cancers rather than viewing it as a single, isolated tumor type.
Limitations: Narrative review that does not present original experimental or clinical data.; Abstract emphasizes heterogeneity and diagnostic challenges, which limit definitive clinical recommendations.; No quantitative synthesis or meta-analysis is reported in the abstract.; Authors state that readiness for a major change in understanding LCNEC is unresolved and further studies are needed..
AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed
OtherMixed resultsModerate evidenceTier 4 · clinical
Journal of the National Comprehensive Cancer Network : JNCCN · Sep 2025 · Practice Guideline
non-small-cell lung cancer (NSCLC)
This document summarizes recent updates to the NCCN Guidelines for non-small cell lung cancer (NSCLC). The updates focus on systemic therapy options for patients with nonmetastatic NSCLC and on corresponding molecular testing considerations.
Key findings
- The NCCN Guidelines Insights present recent updates for NSCLC management.
- The discussion emphasizes systemic therapy options for nonmetastatic NSCLC.
- The guidance highlights molecular testing considerations that correspond to systemic therapy choices.
Limitations: Abstract provides no details on specific therapies, recommended regimens, or testing algorithms.; No primary data, numerical results, or methods are reported in the abstract.; As a guideline summary, it synthesizes evidence rather than presenting new experimental or clinical trial data..
AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed
Animal studyReported positivePreclinical onlyTier 2 · animal
Cell reports · Aug 2025 · mouse models and NSCLC cell lines; gut microbiota comparison in patients with NSCLC and healthy controls
This study looked at gut bacteria and a bacterial metabolite in non-small cell lung cancer. The authors found that Bifidobacterium animalis was lower in patients with NSCLC, and in mouse models and cell lines it was associated with less tumor progression. They identified indole-3-acetic acid as a key metabolite and reported that it affected AHR/METTL3/STAT3 signaling and immune cells in ways linked to reduced tumor growth.
Key findings
- Bifidobacterium animalis was markedly decreased in patients with NSCLC compared with healthy controls.
- B. animalis suppressed tumor progression in two NSCLC mouse models and NSCLC cell lines.
- Indole-3-acetic acid was identified as the pivotal metabolite of B. animalis with anti-NSCLC properties.
- B. animalis and IAA activated AHR and suppressed METTL3 and STAT3 m6A methylation.
- B. animalis and IAA reduced M2 macrophage polarization and enhanced CD8+ T cell functions by suppressing IL-6.
Limitations: Preclinical findings dominate the study; the anticancer effects were shown in mouse models and cell lines, not in a human trial.; Human data were observational/comparative microbiome profiling only, so causality cannot be established.; The abstract does not provide sample sizes, doses, or follow-up duration.; The abstract does not report clinical outcomes in patients..
The study links a gut bacterium and its metabolite to NSCLC progression and antitumor immunity in preclinical models.
AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed
Human · observationalMechanismMixed resultsLimited evidenceTier 3 · early humann = 590
Nature communications · Aug 2025 · cohort study (two independent clinical/genomic cohorts)
pulmonary large cell neuroendocrine carcinoma (LCNEC)small cell lung cancer (SCLC)non-small cell lung cancer (NSCLC)
The authors analyzed clinical and molecular data from 590 patients with pulmonary large cell neuroendocrine carcinoma across two cohorts. They identified two genomic subtypes (NSCLC-like with KEAP1/KRAS/STK11 mutations and SCLC-like with RB1/TP53 mutations) and report that 80% of tumors aligned with SCLC transcriptional profiles. The study found elevated FGL-1 and SPINK1 expression in NSCLC-like LCNECs and higher DLL3 in SCLC-like LCNECs, and noted fewer tumor-infiltrating lymphocytes in LCNEC compared with other lung cancers. Overall survival was comparable across chemotherapy, chemoimmunotherapy, and immunotherapy in this cohort.
Reported effect: proportion aligning with SCLC transcriptional profiles 80%, n=590
Key findings
- Study cohort: 590 patients across two independent cohorts.
- Comparable overall survival across treatment regimens (chemotherapy, chemoimmunotherapy, immunotherapy) without unexpected adverse events.
- Genomic analysis identified two LCNEC subtypes: NSCLC-like (KEAP1, KRAS, STK11 mutations) and SCLC-like (RB1, TP53 mutations).
- 80% of LCNEC tumors aligned with SCLC transcriptional profiles.
- Serial sampling showed stable mutational landscapes but shifting transcriptomic profiles over time.
- Elevated FGL-1 (a LAG-3 ligand) and SPINK1 expression were observed in NSCLC-like LCNECs; DLL3 levels were higher in SCLC-like LCNECs.
- Immunofluorescence confirmed FGL-1 expression in NSCLC-like LCNECs.
- H&E analyses indicated fewer tumor-infiltrating lymphocytes in LCNECs versus other lung cancers.
- Authors suggest these immunogenomic features support future investigation of LAG-3, SPINK1, and DLL3-targeted approaches.
Limitations: Observational cohort design — no randomized comparison of treatments reported in the abstract.; Abstract provides no quantitative survival or subgroup outcome measures (no effect sizes or statistical details reported).; Molecular associations (expression of FGL-1, SPINK1, DLL3) are descriptive and do not demonstrate therapeutic efficacy.; Functional or clinical validation of proposed targets is not presented in the abstract.; H&E-based assessment of tumor-infiltrating lymphocytes is a histologic surrogate and may lack detailed immunophenotyping..
Identifies immunogenomic subtypes and candidate targets (FGL-1/LAG-3, SPINK1, DLL3) in LCNEC that may guide future therapeutic investigations.
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
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
ReviewFormulationReported positiveLimited evidenceTier 4 · clinical
Small methods · Jul 2025 · review
non-small cell lung cancer
This is a review article summarizing how nanomedicines are being developed to support immunotherapy for non-small cell lung cancer. The authors survey core features and the current clinical status of strategies such as immune checkpoint blockade, antibody-drug conjugates, cell engagers, adoptive cells, and cancer vaccines, and emphasize recent nanomedicine developments that may boost these approaches. The abstract highlights advantages of nanomedicines including tumor targeting, improved bioavailability, reduced systemic toxicity, and potential to overcome immune resistance. No new experimental data or quantitative results are reported in the abstract.
Studied with: immune checkpoint blockade, antibody-drug conjugates, cell engagers, adoptive cells, cancer vaccines.
Key findings
- Nanomedicines may offer advantages including specific targeting of tumor cells, improved drug bioavailability, reduced systemic toxicity, and overcoming of immune resistance.
- The review surveys the core features and current clinical status of NSCLC immunotherapy strategies: immune checkpoint blockade, antibody-drug conjugates, cell engagers, adoptive cells, and cancer vaccines.
- Particular emphasis is placed on recent developments of nanomedicines that boost these immunotherapy strategies.
Limitations: This is a review article; no new experimental or clinical trial data are presented in the abstract.; Abstract provides no quantitative results, sample sizes, doses, or outcome metrics.; Species, specific clinical trial identifiers, and funding sources are not specified in the abstract..
AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed
Human · observationalMixed resultsLimited evidenceTier 3 · early humann = 11310
Lung cancer (Amsterdam, Netherlands) · Jun 2025 · prospective registry study (Japanese Joint Committee of Lung Cancer Registry)
large cell neuroendocrine carcinomasmall cell lung cancersquamous cell carcinomaadenocarcinoma
This prospective registry study analyzed 11,310 Japanese lung cancer patients (80 with LCNEC) from January 2012 to April 2016 to compare clinical characteristics, chemotherapy response, and survival across histologies. LCNEC patients were mostly older male smokers and had lower overall response and disease control rates to first-line cisplatin- or carboplatin-based chemotherapy in stage IV disease compared with SCLC. Three-year survival was similar between LCNEC (14.2%) and SCLC (15.9%), and Cox analysis showed no statistically significant difference in overall survival (HR 0.818, 95% CI 0.611-1.096, p = 0.178).
Reported effects: cohort_size 11310, n=11310 · LCNEC_count 80, n=80 · +9 more
Key findings
- Total cohort: 11,310 patients from the JJCLCR database.
- In total, 80 patients (0.7%) were diagnosed with LCNEC.
- LCNEC patients had median age 68 years, 93.8% men, and 97.5% smokers.
- In stage IV patients, best overall response and disease control rates for first-line cisplatin-based chemotherapy were 34.8% and 43.5% for LCNEC but 60.6% and 69.7% for SCLC.
- For first-line carboplatin-based chemotherapy in stage IV patients, overall response and disease control rates were 29.4% and 41.2% for LCNEC, but 56.1% and 68.4% for SCLC.
- The 3-year survival rates were 14.2% for LCNEC, 15.9% for SCLC, 17.8% for squamous cell carcinoma, and 27.1% for adenocarcinoma.
- Cox hazard analysis comparing overall survival between LCNEC and SCLC showed hazard ratio 0.818 (95% CI 0.611-1.096, p = 0.178), not statistically significant.
Limitations: Small number of LCNEC cases (80) relative to the full registry cohort.; Observational registry design without randomized treatment assignment.; Potential heterogeneity in treatments and management across registry sites.; Follow-up limited to registry period (opened Jan 2012; completed Apr 2016) with no median follow-up duration reported in the abstract..
AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed
Case reportMixed resultsLimited evidenceTier 3 · early humann = 1
JTO clinical and research reports · Jul 2024 · case report
large cell neuroendocrine carcinoma of the lung
A 20-year-old man with metastatic large cell neuroendocrine carcinoma of the lung received tarlatamab, a DLL3-targeting bispecific T-cell engager. Treatment was complicated by transient cytokine release syndrome and resulted in a partial response. The authors state that bispecific T-cell engagers may offer a novel treatment approach for this cancer.
Key findings
- A 20-year-old man with metastatic large cell neuroendocrine carcinoma of the lung was treated with tarlatamab.
- Treatment was complicated by transient cytokine release syndrome.
- Treatment resulted in a partial response.
- Authors suggest bispecific T-cell engagers may offer a novel treatment approach for large cell neuroendocrine carcinoma of the lung.
Limitations: Single-patient case report (n=1).; No control or comparator provided.; Dose, treatment schedule, and duration of follow-up are not reported in the abstract.; Findings cannot be generalized from one case.; Safety data limited to a single transient cytokine release syndrome event with no longer-term safety outcomes reported..
AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed · Full text
Animal studyReported positivePreclinical onlyTier 2 · animal
Signal transduction and targeted therapy · Jul 2024
lung adenocarcinomaprostate adenocarcinomasmall cell carcinoma (lung and prostate)neuroendocrine transformation
The study tested CDC7 inhibition with simurosertib in models of neuroendocrine (NE) transformation in lung and prostate tumors. In in vivo models, CDC7 inhibition suppressed NE transdifferentiation and extended responses to targeted therapy and to cytotoxic drugs by inducing proteasome-mediated degradation of the MYC oncoprotein; a degradation-resistant MYC isoform reversed this effect.
Studied with: targeted therapy (unspecified), cisplatin, irinotecan.
Key findings
- CDC7 is upregulated during the initial steps of neuroendocrine transformation after TP53/RB1 co-inactivation.
- CDC7 inhibition with simurosertib suppressed NE transdifferentiation and extended response to targeted therapy in in vivo models of NE transformation.
- CDC7 inhibition induced proteasome-mediated degradation of MYC, implicated in stemness and histological transformation.
- Ectopic overexpression of a degradation-resistant MYC isoform reestablished the NE transformation phenotype even in the presence of simurosertib.
- CDC7 inhibition markedly extended response to standard cytotoxics (cisplatin, irinotecan) in lung and prostate small cell carcinoma models.
- Authors propose CDC7 inhibition as a strategy to constrain lineage plasticity and to treat NE tumors; simurosertib clinical trials are ongoing (not reported in this study).
Limitations: All reported experiments are preclinical (in vivo models); no human trial data are presented in this abstract.; The abstract does not report sample sizes, doses, or detailed experimental parameters.; Species and detailed model descriptions are not specified in the abstract.; Safety, toxicity, and clinical efficacy in patients are not addressed in this study..
AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed · Full text
ReviewMechanismReported positivePreclinical onlyTier 4 · clinical
Frontiers in immunology · May 2024
non-small cell lung carcinomalung neoplasmsnon-small cell lung cancer (NSCLC)
This is a review summarizing studies on extracellular vesicles (EVs) in non-small cell lung cancer (NSCLC). It describes how EVs produced by cancer stem cells may promote stem-like traits, tumor progression and metastasis, and discusses implications for developing NSCLC biomarkers and strategies to target the cancer stem cell niche.
Key findings
- EVs are membrane-bound nanoparticles secreted by cells that carry messages for intercellular communication.
- Numerous studies have implicated NSCLC cancer stem cell (CSC)-derived EVs in factors associated with NSCLC lethality.
- EV-directed cross-talk between CSCs and cells of the tumor microenvironment promotes stemness, tumor progression and metastasis in NSCLC.
- Mechanistic studies provide insights for developing novel diagnostic and prognostic biomarkers and strategies to therapeutically target the NSCLC CSC niche.
Limitations: This article is a review and does not present new experimental data.; The abstract indicates a focus on mechanistic studies, which are likely preclinical (in vitro or animal) rather than validated clinical evidence.; The abstract does not describe clinical validation of the proposed biomarkers or therapeutic strategies..
AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed · Full text
ReviewTrialInconclusiveModerate evidenceTier 4 · clinical
Journal of the National Comprehensive Cancer Network : JNCCN · May 2024 · practice guideline
non-small cell lung cancer
This NCCN guideline update summarizes treatment recommendations for people with advanced or metastatic non-small cell lung cancer who have actionable molecular biomarkers. It notes that the panel updated the list of recommended targeted therapies based on recent FDA approvals and clinical data. The abstract does not report results from a single intervention study or any quantitative outcomes.
Key findings
- The guideline focuses on advanced or metastatic NSCLC with actionable molecular biomarkers.
- Recommended targeted therapies were updated based on recent FDA approvals and clinical data.
- No specific drug, dose, or outcome data are provided in the abstract.
Limitations: This is a practice guideline summary, not an original clinical study.; The abstract does not name the specific targeted therapies or biomarkers.; No efficacy, safety, or survival results are reported in the abstract..
Provides guideline recommendations for targeted therapy in advanced/metastatic NSCLC rather than testing a single repurposed drug or natural compound.
AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed
ReviewMechanismInconclusiveLimited evidenceTier 4 · clinical
Frontiers in medicine · Feb 2024
pulmonary large cell neuroendocrine carcinoma (LCNEC)small cell lung cancer (SCLC)
This narrative review summarizes current knowledge on diagnosis, molecular characteristics, and treatment strategies for pulmonary large cell neuroendocrine carcinoma (LCNEC). The authors state LCNEC is a high-grade neuroendocrine carcinoma (about 3% of primary lung cancer) with strong invasion, high heterogeneity, and very poor prognosis, and that diagnosis and treatment remain controversial and often refer to small cell lung cancer strategies. They note recent genetic analyses and emerging clinical trials provide increasing evidence to support more precise diagnosis and therapy and outline directions for future work.
Key findings
- LCNEC is a high-grade neuroendocrine carcinoma accounting for approximately 3% of primary lung cancer.
- LCNEC is characterized by strong invasion, high heterogeneity, and extremely poor prognosis.
- Diagnosis and treatment of LCNEC are controversial and currently often follow therapeutic strategies for SCLC rather than LCNEC-specific precision therapies.
- Recent genetic analyses and clinical trials of LCNEC have begun to emerge, offering more evidence to inform precise diagnosis and treatment.
- This review summarizes diagnosis, molecular characteristics, and treatment and suggests potential directions for future LCNEC diagnosis and treatment research.
Limitations: Narrative review article that presents synthesis rather than original experimental or clinical data.; Abstract provides no methodological details (e.g., search strategy, inclusion criteria) so it is unclear whether this is a systematic review.; No quantitative synthesis, primary outcome data, or novel trial results are reported in the abstract.; Conclusions are general and the abstract lacks specific molecular findings or treatment outcome metrics..
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
Pharmaceuticals (Basel, Switzerland) · Feb 2024
non-small cell lung cancer
This is an editorial about non-small cell lung cancer (NSCLC) that states NSCLC management remains a major challenge and a global health burden. The article title indicates it discusses advances and a paradigm shift in NSCLC treatment, but the provided abstract text is truncated and contains no original data or detailed findings.
Key findings
- The piece is an editorial discussing challenges in NSCLC management.
- The title indicates the article addresses advances and a paradigm shift in NSCLC treatment.
- No original experimental or clinical data are provided in the available abstract text.
Limitations: Article is an editorial (no primary research data).; Provided abstract text is truncated and contains insufficient detail (no methods, results, or quantitative findings).; Cannot extract details on interventions, doses, populations, or outcomes 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
ReviewMechanismMixed resultsLimited evidenceTier 4 · clinical
Mutation research · Jan 2024 · narrative review
Cisplatinnon-small-cell lung cancerlung cancerNSCLC This narrative review summarizes platinum-based targeted chemotherapies in non-small-cell lung cancer (NSCLC), with a focus on cisplatin. It describes the NSCLC tumor microenvironment, cisplatin's mechanism of action, mechanisms of cisplatin resistance in NSCLC, and strategies proposed to reverse that resistance.
Key findings
- Lung cancer is highly prevalent and has a poor prognosis; NSCLC recurrences are common after surgery.
- Cisplatin is described as the more active platinum drug recommended for patients with advanced NSCLC and for early-stage patients needing adjuvant therapy.
- The review covers the NSCLC microenvironment, treatment approaches, cisplatin mechanism of action, cisplatin resistance in NSCLC, and prevention strategies to revert drug resistance.
Limitations: Narrative review — no original experimental or clinical data are presented in the abstract.; Abstract does not describe review methods (e.g., search strategy, inclusion criteria) or any quantitative synthesis.; No numeric clinical outcomes or trial results are reported in the abstract..
AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed