ReviewInconclusiveLimited evidenceTier 4 · clinical
Therapeutic advances in medical oncology · Dec 2025 · review
epithelial ovarian cancerhigh-grade serous ovarian cancerovarian clear cell carcinomaendometrioid ovarian carcinomamucinous ovarian carcinomalow-grade serous ovarian carcinomaovarian carcinosarcoma
This review describes the main genomic subtypes of epithelial ovarian cancer and how those differences may help match patients to targeted therapies. It highlights PARP inhibitors, MAPK pathway inhibitors, cell cycle checkpoint inhibitors, immune checkpoint inhibitors, and antibody-drug conjugate approaches that are being investigated for specific ovarian cancer types. The article also notes that resistance to PARP inhibitors remains a problem and that more evidence is needed for effective combination therapies.
Key findings
- High-grade serous ovarian cancer is linked mainly to homologous recombination repair gene alterations such as BRCA1 and BRCA2.
- Ovarian clear cell carcinoma is associated with ARID1A and PIK3CA alterations; endometrioid ovarian carcinoma with PIK3CA and KRAS; mucinous ovarian carcinoma with CDKN2A and KRAS; and low-grade serous ovarian carcinoma with MAPK pathway genes such as BRAF and KRAS.
- PARP inhibitor therapy has improved survival for women with homologous recombination repair defects in high-grade serous ovarian cancer, but acquired resistance remains an issue.
- The review emphasizes that genomically targeted combination therapies are urgently needed and that some reported responses are preliminary.
Limitations: Review article only; no new experimental or clinical data presented in the abstract.; No quantitative outcomes or effect sizes are reported in the abstract.; The abstract is broad and does not provide trial-level details, sample sizes, or follow-up durations.; Some therapies discussed are preliminary and require further evidence..
The article is about ovarian cancer genomics and targeted therapies, not a single compound experiment.
AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed · Full text
Human · observationalMixed resultsLimited evidenceTier 3 · early humann = 26
Frontiers in oncology · Jun 2025 · single-center retrospective study
ovarian carcinosarcoma
This single-center retrospective study reviewed 26 patients with ovarian carcinosarcoma treated between March 2012 and October 2023 and recorded baseline features, treatments, and survival. Median progression-free survival (PFS) for the cohort was 17.53 months. Several clinical/pathologic features (ascites ≥500 ml, age ≥58, tumor diameter <10 cm, Ki-67 ≥70%) showed trends toward longer PFS but the reported comparisons were not statistically significant. Four homologous recombination deficiency (HRD)-positive patients who received a PARP inhibitor had a median PFS of 22.68 months.
Reported effects: median PFS (all patients) 17.53 mo, n=26 · PFS, ascites ≥500 ml vs <500 ml 27.83 mo, p p=0.12 · +8 more
Key findings
- Twenty-six patients met inclusion criteria; the median PFS of all enrolled patients was 17.53 months.
- Patients with ascites ≥500 ml had PFS 27.83 months vs. 13.7 months (p=0.12, HR 0.72), showing a trend toward better prognosis.
- Patients age ≥58 years had PFS 22.93 months vs. 13.53 months (p=0.354, HR 0.62), showing a trend toward better prognosis.
- Patients with tumor diameter <10 cm had PFS 27.83 months vs. 12.80 months (p=0.095, HR 0.36), showing a trend toward better prognosis.
- Patients with Ki-67 ≥70% had PFS 22.93 months vs. 13.53 months (p=0.093, HR 0.39), showing a trend toward better prognosis.
- Five patients underwent genetic testing; 4 were HRD-positive and treated with a PARP inhibitor. The median PFS of those 4 patients was 22.68 months.
Limitations: Small overall sample size (n=26); Single-center, retrospective design with potential for selection and information bias; Very small genetic-testing subgroup (5 tested; 4 HRD-positive) limits conclusions about PARP inhibitor outcomes; Reported subgroup comparisons showed p-values > 0.05 (described as trends) and thus were not statistically significant; No randomized or controlled comparison reported in the abstract; No details on PARP inhibitor dosing, duration, or toxicity provided in the abstract.
AI summary of the abstract, human-reviewed · Jul 2026. Describes what this study reported, not medical advice. View on PubMed · Full text
Human · observationalMechanismReported positiveLimited evidenceTier 3 · early humann = 8
The American journal of surgical pathology · May 2025 · case series with clinicopathologic evaluation and next-generation sequencing
gynecologic carcinosarcomaendometrial carcinosarcomalower uterine segment carcinosarcomaovarian carcinosarcoma
The authors report a clinicopathologic and genomic analysis of eight gynecologic carcinosarcomas with a mesonephric-like carcinomatous component. Sequencing (done separately for carcinomatous and sarcomatous parts in some tumors) showed identical single-nucleotide variants between components, low tumor mutational burden (<10 mutations/Mb), microsatellite stability, and KRAS codon 12 mutations in all sequenced cases. Additional alterations (eg, PTEN, PIK3CA, ARID1A) were identified in several tumors. This is a small descriptive case series and does not include functional experiments or outcome correlations beyond staging.
Reported effects: n_cases 8, n=8 · mean_age 65.6 · +11 more
Key findings
- Eight cases of gynecologic MLCS (endometrial, lower uterine segment, and ovarian) were identified and evaluated.
- Genomic DNA extraction and NGS were performed separately on carcinomatous and sarcomatous components of 4 tumors and on combined components of 2 tumors.
- The carcinomatous and sarcomatous components were observed to harbor the same single nucleotide variations when sequenced separately.
- All cases had less than 10 mutations/Mb and were microsatellite stable.
- All sequenced cases (6/6, 100%) harbored KRAS point mutations in codon 12 (p.G12D n=2; p.G12A n=2; p.G12V n=2).
- Five cases showed additional alterations including ARID1A, PTEN, PIK3CA, SPOP, TET1, BUB1, LYN and PTPRD.
- Authors suggest the combination of KRAS and PTEN/PIK3CA alterations is consistent with combined endometrioid and mesonephric differentiation in MLCS.
Limitations: Small sample size (8 cases) limits generalizability.; Only 6 tumors underwent NGS (4 separately by component, 2 combined), so not all cases had component-specific sequencing.; Descriptive molecular profiling without functional validation of mutations.; No survival or treatment-outcome correlations reported beyond FIGO stage..
AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed
Human · observationalReported positiveLimited evidenceTier 3 · early humann = 10
BMC cancer · Dec 2024 · retrospective cohort
Trastuzumab-deruxtecan-t-dxdTrastuzumab-deruxtecanendometrial neoplasmsovarian neoplasmscervical neoplasmsuterine carcinosarcomauterine leiomyosarcomauterine serous carcinomaovarian carcinosarcomahigh-grade serous ovarian carcinomamucinous ovarian carcinomasquamous cervical carcinoma This retrospective single-center study identified 10 patients with HER2-expressing (IHC 2+/3+) recurrent or metastatic gynecological cancers who received trastuzumab deruxtecan (5.4 mg/kg IV every 3 weeks). The cohort had a median progression-free survival of 5.4 months (95% CI 0.8-9.8). Five patients had a partial response, one had stable disease at 12 weeks, and four had disease progression at initial assessment. Clinical benefit was observed mainly in tumors with HER2 IHC 3+.
Reported effects: median PFS 5.4 mo [0.8–9.8], n=10 · partial responses 5, n=10 · +2 more
Key findings
- 10 patients with recurrent/metastatic HER2-expressing gynecological malignancies were treated with T-DXd.
- Histologies included uterine neoplasms (n=5), cervical squamous carcinoma (n=1) and ovarian cancers (n=4).
- Median age was 65.4 years (25th-75th percentile, 58.1-75.2 years).
- HER2 by IHC: 5 patients were 3+ and 5 patients were 2+.
- Median number of prior therapy lines was 4 (range 2-6); 2 uterine serous carcinoma patients were pretreated with trastuzumab and 4 patients had prior immunotherapy.
- Dose: T-DXd 5.4 mg/kg IV every 3 weeks until progression/toxicity.
- Median progression-free survival (PFS) in the cohort was 5.4 months (95% CI 0.8-9.8 months).
- Responses: 5 patients had partial response (including 2 previously treated with trastuzumab), 1 patient had stable disease at 12 weeks, 4 patients had disease progression at initial assessment.
- Most patients who derived clinical benefit had HER2 IHC 3+ expression.
Limitations: Retrospective, single-center design; Very small sample size (n=10); No control or comparator arm; Heterogeneous mix of gynecologic histologies; Heavily pre-treated population limits generalizability; Limited/absent reporting of safety or adverse event data in the abstract; Potential selection and reporting bias inherent to retrospective series.
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 = 32
Virchows Archiv : an international journal of pathology · Dec 2024 · targeted next-generation sequencing of tumor specimens (molecular profiling)
tubo-ovarian carcinosarcoma
The authors performed targeted next-generation sequencing of 32 tubo-ovarian carcinosarcoma specimens (including 7 serous effusions) covering 50 genes. They found 31 mutations in 25 of 32 tumors, with TP53 alterations predominant (25 mutations in 24 tumors); other mutations (RB1, MET, KRAS, PTEN, KIT) were rare. Patient-matched specimens shared the same TP53 mutation, and specimens with no detected mutations were more frequent among serous effusions than surgical specimens. The authors conclude TP53 mutations dominate the molecular landscape and note it is uncertain whether effusion-derived cells differ from solid lesions.
Reported effects: specimens_n 32, n=32 · patients_n 25, n=25 · +11 more
Key findings
- Specimens (n=32) consisted of 25 biopsies/surgical resection specimens and 7 serous effusions (6 peritoneal, 1 pleural) from 25 patients.
- Targeted next-generation sequencing covered 50 unique genes.
- A total of 31 mutations were found in 25 of the 32 tumors studied, of which 1 had 3 mutations, 4 had 2 different mutations, and 20 had a single mutation.
- The most common mutations were in TP53 (n=25 in 24 tumors; 1 tumor with 2 different mutations).
- Less common mutations were found in RB1 (n=2), MET (n=1), KRAS (n=1), PTEN (n=1), and KIT (n=1).
- Patient-matched specimens harbored the same TP53 mutation.
- Tumors with no detected mutations were more common in serous effusion specimens (3/7; 43%) compared with surgical specimens (4/25; 16%).
Limitations: Small sample size (32 specimens from 25 patients).; Use of a targeted 50-gene panel limits detection to predefined genes and may miss other relevant alterations.; Observational molecular profiling without functional validation of variants.; Unclear generalizability given limited anatomic sampling and small number of effusion specimens..
AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed · Full text
Human · observationalMechanismReported positiveModerate evidenceTier 3 · early humann = 122
Histopathology · Nov 2024 · immunohistochemical analysis of a cohort of human tumours (122 cases) including STK11 adnexal tumours and morphological mimics
STK11 adnexal tumourovarian neoplasmsovarian endometrioid carcinomatubo-ovarian high-grade serous carcinomaovarian mesonephric-like adenocarcinomaovarian carcinosarcomaperitoneal malignant mesotheliomapelvic plexiform leiomyomaovarian solid pseudopapillary tumourgranulosa cell tumourSertoli-Leydig cell tumourLeydig cell tumourSertoli cell tumoursteroid cell tumourfemale adnexal tumour of Wolffian originextra-ovarian sex cord-stromal tumour
Researchers performed STK11 (LKB1) immunohistochemistry on 122 human tumour samples, including 17 STK11 adnexal tumours and 105 morphological mimics. All 17 STK11 adnexal tumours showed complete loss of cytoplasmic STK11 staining. Nearly all other tumour types retained cytoplasmic STK11 staining, with the exception of one endometrioid carcinoma with mucinous differentiation showing complete loss and one high-grade serous carcinoma showing subclonal loss. The authors conclude STK11 IHC is a highly sensitive and specific marker for distinguishing STK11 adnexal tumour in the appropriate morphological context and could obviate confirmatory molecular testing.
Reported effects: total tumours tested 122, n=122 · STK11 adnexal tumours included 17, n=17 · +3 more
Key findings
- IHC for STK11 was performed on 122 tumours, including 17 STK11 adnexal tumours and 105 morphological mimics (full list of mimics given in abstract).
- All STK11 adnexal tumours showed complete loss of cytoplasmic staining for STK11.
- All other tumour types showed retained cytoplasmic staining, except for one endometrioid carcinoma with mucinous differentiation which showed complete loss of STK11 expression and a high-grade serous carcinoma with subclonal loss.
- Authors conclude STK11 IHC is a highly sensitive and specific immunohistochemical marker for distinguishing STK11 adnexal tumour from histological mimics and may obviate the need for confirmatory molecular studies in the appropriate morphological context.
Limitations: Small number of STK11 adnexal tumours (n=17), reflecting rarity of the entity.; Study reports a single cohort with no external validation cohort mentioned in the abstract.; Potential selection bias because tumour types were a selected set of morphological mimics.; Abstract does not report blinding, interobserver reproducibility, or diagnostic performance statistics (sensitivity/specificity values) beyond descriptive counts.; Two non-STK11 tumours showed loss/subclonal loss of STK11, indicating imperfect specificity in this cohort..
AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed · Full text