Novel therapeutics for platinum-resistant ovarian cancer: from biological mechanisms to emerging biomarker-guided strategies

For decades, platinum resistance has remained one of the major barriers to improving outcomes in ovarian cancer. Patients with platinum-resistant ovarian cancer (PROC) generally have shorter overall survival and lower response rates to second-line treatment than those with platinum-sensitive disease. In recent years, innovative therapeutics have emerged for PROC, including antibody-drug conjugates (ADCs), immune checkpoint inhibitors (ICIs), DNA-damage response (DDR) agents, and other rational combination regimens. However, a clinically oriented review integrating the biological basis and clinical applications of these approaches is still lacking. In this review, we summarize the evolving therapeutic landscape of PROC from the following perspectives: (1) the current mechanisms underlying platinum resistance, (2) ADCs targeting FRɑ, HER2, TROP2, CDH6, and other cell surface antigens, (3) immune checkpoint inhibitors and emerging immunotherapy-based combinations, (4) therapeutic strategies targeting the DNA damage repair pathway, (5) anti-angiogenic therapies, and (6) other investigational approaches. We integrate the preclinical and clinical evidence, with particular emphasis on treatment efficacy, patient selection, and targeted biomarkers. By connecting mechanistic insights with clinical development, this review aims to provide a practical framework for treatment decision-making and to identify priorities for future translational research in PROC.