In The Know-August 2025

August 2025

Pdf Summary

The August 2025 edition of Ed’s List provides a comprehensive overview of significant recent research in gynecologic oncology, focusing mainly on ovarian, endometrial, and cervical cancers, as well as advancements in cancer screening, treatment, and genetic predisposition analysis.

Key findings include:

1. <strong>Ovarian Cancer Therapeutics and Biology</strong>: Sequential treatment using PARP and WEE1 inhibitors shows enhanced antitumor immune responses and improved T-cell viability in ovarian cancer models. Novel therapies such as the combination of avutometinib and defactinib exhibit promising efficacy in recurrent low-grade serous ovarian cancer, particularly in KRAS-mutant tumors. Additionally, allogeneic CAR-NKT cells demonstrate superior anti-ovarian cancer efficacy with reduced toxicity compared to traditional CAR-T cells, highlighting potential for off-the-shelf immunotherapy. A new 161Tb-based anti-L1CAM radioimmunotherapy targets ovarian cancer stem cells more effectively than previous approaches. Molecular studies reveal that SMARCA4 loss in small cell carcinoma of the ovary leads to RNA polymerase II pausing, elevated R-loops, and compromised BRCA1-mediated DNA repair, sensitizing tumors to PARP inhibitors.

2. <strong>Genetic Predisposition and Screening</strong>: Large population-based analyses confirm the association of pathogenic variants in cancer predisposition genes (including BRCA1/2, RAD51C/D, BRIP1) with single and multiple cancer diagnoses, supporting multigene panel testing. A comprehensive screening program successfully detected early-stage cancers among individuals with genetic predisposition, emphasizing tailored screening benefits. Novel biomarkers, including lipidomics combined with protein markers and machine learning, show promise for early detection of ovarian cancer in symptomatic populations.

3. <strong>Endometrial and Cervical Cancer Management</strong>: ESGO/ESTRO/ESP updated guidelines incorporate molecular classification improving preoperative risk stratification in endometrial cancer. In cervical cancer, a phase II trial shows that camrelizumab combined with famitinib enhances objective response rates and progression-free survival in recurrent/metastatic cases. Modeling studies from South Korea suggest that high-risk HPV testing combined with increased HPV vaccination rates could accelerate cervical cancer elimination by as early as 2034.

4. <strong>Cancer Screening and Prevention</strong>: Research highlights missed preventive opportunities in salpingectomy during surgeries prior to high-grade serous carcinoma diagnosis, suggesting a need for improved surgical practices. County-level disparities in cervical cancer screening contribute to incidence and mortality differences.

Overall, the gathered studies underscore the ongoing progress toward personalized therapies, improved early detection, and prevention strategies in gynecologic cancers to improve outcomes.

Keywords

Ovarian Cancer Therapeutics

PARP and WEE1 Inhibitors

CAR-NKT Cells Immunotherapy

161Tb-based Radioimmunotherapy

SMARCA4 and DNA Repair

Genetic Predisposition Genes

Multigene Panel Testing

Endometrial Cancer Molecular Classification

Cervical Cancer Immunotherapy

Cancer Screening and Prevention