Mariano Laguna-Olmos

The Role of Microbiota in Ovarian Cancer: Implications for Treatment Response and Therapeutic Strategies

Cancer remains a global health challenge (18.1 million new cases in 2020), with incidence projected to reach 28 million within two decades. Ovarian cancer (OC) is the deadliest gynecologic malignancy, usually diagnosed at advanced stages and with poorly understood etiology. Emerging evidence implicates reproductive tract and gut microbiota in OC biology. Microbiota shape carcinogenesis via turnover, immunity, and metabolism; dysbiosis promotes DNA damage, inflammation, and carcinogenic metabolites, engaging multiple hallmarks of cancer. In OC, microbes may reach tumors by local ascent, translocation, or hematogenous spread, originating from vagina, upper reproductive tract, peritoneal fluid, or gut. Lactobacillus-dominant vaginal communities support mucosal integrity, whereas anaerobes disrupt barriers, increase inflammation, and correlate with OC risk; mouse models show vaginal dysbiosis accelerates tumor progression. Distinct microbial profiles in upper reproductive sites and peritoneal fluid associated with immune remodeling. Gut dysbiosis drives barrier loss, immune imbalance, and estrogen reactivation. Microbial metabolites (lipopolysaccharides, short-chain fatty acids) modulate oncogenic pathways, altering epithelial–mesenchymal transition, immune evasion, and drug resistance. Across cohorts, OC tissues and fluids show Pseudomonadota/Bacteroidota enrichment and Akkermansia depletion; fecal microbiota from OC patients accelerates tumor growth in mice, whereas Akkermansia supplementation restores antitumor immunity. Antibiotic exposure and platinum resistance associate with reduced diversity and expansion of lactate-producing taxa. Microbiome-informed interventions–diet, probiotics/postbiotics, fecal microbiota transfer, and selective antibiotics–may augment chemotherapy and immunotherapy. Overall, the microbiome is a modifiable determinant of OC risk, progression, and treatment response, warranting rigorous, standardized, multi-omics studies.

Prognostic significance of molecular classification in high-risk endometrial cancer patients undergoing sentinel lymph node mapping

The adoption of selective sentinel lymph node biopsy (SLNB) as a viable alternative to lymphadenectomy, along with the redefinition of nodal risk groups based on molecular classification, has significantly changed the management of early-stage, high-risk preoperative endometrial cancer. A retrospective, multicenter study was conducted under the auspices of the Spanish Gynecologic Oncology Group to evaluate recurrence rates and oncologic outcomes in patients stratified by molecular risk. Three groups were compared: SLNB alone (G1), SLNB combined with pelvic and/or para-aortic lymphadenectomy (G2), and pelvic and/or para-aortic lymphadenectomy without SLNB (G3). The primary endpoint was recurrence rate; secondary endpoints included disease-free survival (DFS), overall survival (OS), recurrence patterns. A total of 221 patients from 14 centers were included, with a median follow-up of 24.4 months (IQR 17-42). Forty-four patients (19.9 %) experienced recurrence. Relapse rates were 15.4 % in G1, 15.8 % in G2, and 22.2 % in G3 (p = 0.479). DFS rates were 84.6 % in G1, 84.1 % in G2, and 77.8 % in G3 (p = 0.56). OS rates were 94.2 %, 90.9 %, and 92.6 %, respectively (p = 0.651). Among the 44 patients with documented recurrence, seven had nodal recurrences, with only two occurring in the group managed with SLNB alone. In this study, patients with early-stage, high-risk preoperative endometrial cancer-classified by molecular subgroups-showed no significant differences in relapse rates, disease-free survival, or overall survival across the three management strategies. Further prospective studies with longer follow-up are warranted to validate these preliminary findings.