Ovarian Cancer Stem Cells: Mechanisms of Progression and Therapeutic Strategies

Ovarian cancer is the most lethal gynecological malignancy, with most patients diagnosed at an advanced stage and eventually relapsed after post-platinum-taxane chemotherapy. High intratumoral heterogeneity, extensive peritoneal dissemination, and acquired chemoresistance continue to restrict the clinical benefits of current therapeutic strategies. Increasing evidence indicates that ovarian cancer stem cells (OCSCs), a rare but highly plastic subpopulation characterized by self-renewal, multilineage differentiation, quiescence, tumor-initiating capacity, and intrinsic stress tolerance, play pivotal roles in tumor initiation, metastasis, recurrence, and therapeutic resistance. In this review, we systematically summarize current knowledge regarding the identification and functional characterization of OCSCs and discuss their clinical relevance to disease progression and poor prognosis. We then delineate the multifaceted mechanisms by which OCSCs drive ovarian cancer progression, with particular emphasis on dysregulated stemness-associated signaling networks, adaptive cellular plasticity, metabolic and stress-response programs, and dynamic interactions with the tumor microenvironment. Furthermore, we review emerging therapeutic strategies aimed at eradicating OCSCs and discuss key barriers that hinder their clinical translation. A deeper understanding of OCSC biology may facilitate the development of precise, combination-based strategies to overcome recurrence, reverse therapeutic resistance, and improve long-term outcomes in ovarian cancer patients.