Emilio Lucia

The future of gynecologic oncologic surgery: a narrative review of current surgical trials

Recent advances in gynecologic oncology have driven a paradigm shift toward less invasive, more personalized surgical approaches. This narrative review critically examines key ongoing international trials investigating innovative surgical strategies across vulvar, cervical, ovarian, and endometrial cancers, with a focus on improving oncologic outcomes while minimizing morbidity. In vulvar cancer, trials are exploring the use of neoadjuvant chemotherapy and the replacement of inguinofemoral lymphadenectomy with chemoradiation in selected patients. For cervical cancer, large multicenter randomized trials are evaluating the oncologic safety of minimally invasive hysterectomy, surgical staging for para-aortic disease, and robotic-assisted surgery. In the contest of ovarian cancer, randomized trials are assessing the role of lymphadenectomy in early-stage disease, the optimal timing of cytoreductive surgery (primary versus interval), and the potential benefits of hyperthermic intraperitoneal chemotherapy, even in cases of platinum-resistant recurrence. For endometrial cancer, both observational and interventional studies are investigating sentinel lymph nodes mapping and robotic-assisted hysterectomy as alternatives to traditional staging procedures. Collectively, these trials underscore the growing importance of individualized treatment strategies guided by disease stage, histologic subtype, response to neoadjuvant therapy, and patient-specific factors. While minimally invasive techniques and surgical de-escalation appear promising for selected patient populations, critical questions remain regarding long-term oncologic safety, cost-effectiveness, and the consistency of practice across institutions. This narrative review synthesizes current evidence and outlines how the outcomes of these pivotal studies are expected to influence future guidelines in gynecologic cancer surgery.

Platinum-induced upregulation of ITGA6 promotes chemoresistance and spreading in ovarian cancer

Abstract Platinum (PT)-resistant Epithelial Ovarian Cancer (EOC) grows as a metastatic disease, disseminating in the abdomen and pelvis. Very few options are available for PT-resistant EOC patients, and little is known about how the acquisition of PT-resistance mediates the increased spreading capabilities of EOC. Here, using isogenic PT-resistant cells, genetic and pharmacological approaches, and patient-derived models, we report that Integrin α6 (ITGA6) is overexpressed by PT-resistant cells and is necessary to sustain EOC metastatic ability and adhesion-dependent PT-resistance. Using in vitro approaches, we showed that PT induces a positive loop that, by stimulating ITGA6 transcription and secretion, contributes to the formation of a pre-metastatic niche enabling EOC cells to disseminate. At molecular level, ITGA6 engagement regulates the production and availability of insulin-like growth factors (IGFs), over-stimulating the IGF1R pathway and upregulating Snail expression. In vitro data were recapitulated using in vivo models in which the targeting of ITGA6 prevents PT-resistant EOC dissemination and improves PT-activity, supporting ITGA6 as a promising druggable target for EOC patients.