Targeting VEGF, PARP, and FRα Pathways in Ovarian Cancer: Clinical Advances with Bevacizumab, Rucaparib, and...

Ovarian cancer remains a leading cause of gynecologic cancer-related mortality worldwide, and long-term outcomes with conventional cytotoxic chemotherapy remain limited. The integration of targeted therapies has substantially reshaped treatment paradigms by exploiting key molecular pathways involved in angiogenesis, DNA damage repair, and folate receptor signaling. This review synthesizes evidence from pivotal phase II and III clinical trials, translational studies, and meta-analyses evaluating inhibition of the VEGF, PARP, and folate receptor-alpha (FRα) pathways, with a focus on bevacizumab, rucaparib, and mirvetuximab soravtansine. Across disease settings, these agents have demonstrated clinically meaningful improvements in progression-free survival, durability of response, and tolerability when deployed in biomarker-selected populations. Bevacizumab has shown consistent benefit when combined with platinum-based chemotherapy and as maintenance therapy in advanced disease. PARP inhibitors, including rucaparib, exploit homologous recombination deficiency (HRD) to induce synthetic lethality and are now central to frontline and recurrent treatment strategies for BRCA-mutated and HRD-positive tumors. Mirvetuximab soravtansine has emerged as an effective and well-tolerated option for patients with FRα-high, platinum-resistant ovarian cancer, addressing a longstanding unmet clinical need. Collectively, VEGF-, PARP-, and FRα-targeted therapies have enabled more rational treatment sequencing, informed combination strategies, and personalized clinical decision-making in ovarian cancer. Ongoing efforts to define optimal sequencing, overcome acquired resistance, and refine predictive biomarkers are expected to further enhance the durability and breadth of benefit from targeted therapies and advance precision oncology in gynecologic malignancies.