Oncogenic Mechanisms and Therapeutic Strategies of Phase Separation-Regulated Biomolecular Condensates in Gynecological Cancers

In gynecological cancers (ovarian, cervical, and endometrial cancers), the high dependence on hormone receptor signaling and viral infections like HPV make the intracellular microenvironment highly susceptible to LLPS equilibrium disruption, thereby driving malignant progression.LLPS-driven nuclear condensates can abnormally activate the transcription of oncogenes or regulate alternative splicing, mRNA stability, and translation efficiency through RNA epigenetic modifications (e.g., m6A, m5C), leading to a massive increase in oncogenic protein synthesis.

Furthermore, phase separation strengthens aerobic glycolysis in tumor cells by regulating metabolic enzymes such as PGK1, providing energy for rapid growth and inhibiting ferroptosis. Phase separation also significantly impacts protein homeostasis and stress response: under stress conditions, cancer cells form stress granules (SGs) through LLPS to evade apoptosis.Additionally, condensates formed via LLPS enhance DNA damage repair capabilities or create physical barriers, resulting in resistance to chemotherapy and PARP inhibitors.