Human · observationalMechanismMixed resultsLimited evidenceTier 3 · early humann = 57
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · Apr 2026 · retrospective case series
tubo-ovarian carcinosarcomaovarian carcinosarcomafallopian tube neoplasm
This single-institution study reviewed 57 tubo-ovarian carcinosarcomas with median follow-up of 32.3 months. Most tumors (51/57, 89%) were p53-abnormal; a small subset (5/57, 9%) were p53 wild-type and all five had canonical KRAS codon 12 mutations and distinct endometrioid histology. The authors report the first primary POLE-mutated OCS in a patient with Lynch syndrome. KRAS-mutated tumors occurred at younger ages and lower stage but recurred in 2 of 5 patients.
Reported effects: median_follow_up 32.3 mo, n=57 · 5-year survival stage I/II 71%, n=57 · +9 more
Key findings
- The overall median follow-up period was 32.3 months.
- Five-year survival rates were 71% (stage I/II), 42% (stage III), and 17% (stage IV).
- Fifty-one (89%) tumors were of the p53-abnormal molecular subtype.
- Five (9%) tumors were of no specific molecular subtype, and all 5 of these tumors harbored canonical mutations in KRAS (codon 12).
- The first reported primary POLE-mutated OCS was identified in a patient with Lynch syndrome (assigned as a double-classifier POLE-mutated/mismatch repair-deficient molecular subtype).
- Compared with the p53-abnormal tumors, KRAS-mutated tumors occurred in younger women at lower stages, but did recur in 2 out of 5 (40%) patients.
- KRAS-mutated tumors always showed endometrioid rather than high-grade serous morphology and were usually ER, PR, and WT1 negative.
- Three KRAS-mutated tumors also had at least focal mesonephric-like histology.
Limitations: Single-institution case series (limited generalizability).; Relatively small overall sample size (n=57) and very small KRAS-mutated subgroup (n=5), limiting statistical power and conclusions about that subset.; Retrospective, observational design without experimental/functional validation.; Follow-up median 32.3 months may limit long-term outcome assessment..
AI summary of the abstract, human-reviewed · Sep 2026. Describes what this study reported, not medical advice. View on PubMed
Animal studyMixed resultsPreclinical onlyTier 2 · animal
Journal of experimental & clinical cancer research : CR · Jan 2026 · High-throughput drug screening in organoid models performed in presence of cisplatin or eribulin, with validation of top combinations in OCS cell line, organoid and PDX models including in vivo PDX experiments.
Cisplatinovarian carcinosarcomahigh-grade serous ovarian cancer (HGSOC) The authors performed high-throughput drug screens in ovarian carcinosarcoma (OCS) organoid models and validated top combinations in a unique OCS cell line, organoid and PDX models. Eribulin combined with either an EGFR inhibitor (erlotinib) or a MEK inhibitor (mirdametinib/PD0325901) produced synergistic effects in some in vitro models, and modest survival improvements in vivo, but several PDX models exhibited resistance mechanisms (high ABCB1 expression or KRAS mutation) limiting efficacy.
Reported effects: models_with_synergy 2, n=4 · PDX_models_with_resistance 2, n=3
Studied with: erlotinib, mirdametinib, PD0325901, cisplatin.
Key findings
- High-throughput screens identified eribulin-based combinations as most effective in OCS organoid models, while cisplatin-based combinations were more effective in HGSOC models.
- Eribulin plus erlotinib or eribulin plus a MEK inhibitor (mirdametinib/PD0325901) were the most effective combinations in OCS models, with synergy seen in two out of four models for each combination.
- OCS models appear particularly reliant on EGFR and MAPK signalling in vitro, especially in tumours with TP53 mutation.
- In vivo (PDX) experiments showed only modest survival improvements for eribulin plus erlotinib, and two of three PDX models had resistance mechanisms (high ABCB1 or KRAS activating mutation).
- KRAS-mutant OCS cell lines and organoids were sensitive to dual EGFR/MAPK targeting, with greater synergy when eribulin was added as a third agent.
Limitations: Preclinical study using in vitro organoids, cell lines and PDX models; no human clinical data reported.; Only modest in vivo survival benefit reported.; Synergy was observed in a subset of models (e.g., two of four organoid models), indicating heterogeneity and limited generalizability.; A small number of PDX models were tested (three), and two showed resistance mechanisms limiting efficacy.; No doses, schedules, or safety/toxicity data in humans provided..
AI summary of the abstract, human-reviewed · Sep 2026. Describes what this study reported, not medical advice. View on PubMed · Full text
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