In The Know-December 2025

December 2025
Pdf Summary
This December 2025 edition of Ed’s List highlights significant advances in gynecologic oncology research.<br /><br />Key studies include a molecular profiling analysis of high-grade serous ovarian carcinoma (HGSOC) revealing five tumor clusters with differing inflammation and endogenous retrovirus expression correlating with patient outcomes, identifying immune-related genes and signaling pathways impacting survival.<br /><br />Ultrasonography measurement of endometrial thickness was evaluated in p53 abnormal endometrial cancers, showing that TVUS screening at a 4 mm threshold is unreliable due to false negatives, supporting the need for tissue sampling in symptomatic cases.<br /><br />A novel lipidomic profiling technique using desorption electrospray ionization mass spectrometry imaging effectively distinguished malignant from benign endometrial tissues with high sensitivity and specificity, highlighting dysregulated lipid and protein signaling pathways and identifying potential biomarkers for early detection.<br /><br />A histology-specific natural history model for ovarian cancer subtypes was developed and validated, reproducing incidence, mortality, and staging data, providing a tool for evaluating future screening and intervention impact.<br /><br />Regarding ovarian cancer treatment, higher body mass index was associated with better chemotherapy completion rates in recent cohorts, contrasting with previous dose-capping concerns.<br /><br />The PORTEC-4a trial demonstrated that tailoring adjuvant therapy based on molecular risk profiling in high-intermediate risk endometrial cancer safely reduced overtreatment without compromising vaginal recurrence rates.<br /><br />Two HPV vaccine studies showed that one dose of bivalent or nonavalent HPV vaccine provided noninferior protection against HPV16/18 infection compared to two doses, and quadrivalent HPV vaccination significantly reduced high-grade vulvovaginal lesions, especially when given before age 17.<br /><br />Preclinical investigations identified cannabidiol and Δ9-tetrahydrocannabinol combination as synergistically inhibiting ovarian cancer cell growth via PI3K/AKT/mTOR pathway modulation and PTEN activation.<br /><br />A dual kinase inhibitor, SM08502, combined with PARP inhibitor olaparib overcame PARP inhibitor resistance in high-grade serous ovarian carcinoma models, remodeling the tumor immune microenvironment and extending survival.<br /><br />Additionally, claudin-4 was discovered as a dual regulator of genome stability and immune evasion, with combined targeting enhancing PARP inhibitor efficacy.<br /><br />Other notable insights include obesity-related comorbidities worsening mortality in postmenopausal endometrial cancer survivors, and cost-effectiveness analyses advocating hybrid approaches to genetic risk assessment in primary care.<br /><br />Overall, this comprehensive compilation informs on innovations spanning molecular characterization, diagnostic advancements, targeted therapeutics, vaccine efficacy, and health systems approaches, advancing clinical management and prevention of gynecologic cancers.
Keywords
gynecologic oncology
high-grade serous ovarian carcinoma
molecular profiling
endometrial thickness ultrasonography
lipidomic profiling
ovarian cancer natural history model
body mass index chemotherapy
PORTEC-4a trial
HPV vaccine efficacy
PARP inhibitor resistance