Therapeutic targeting of post-translational modifications in ovarian cancer: mechanisms and clinical applications.

Ovarian cancer is a lethal disease with high mortality due to late diagnosis, recurrence, and chemotherapy resistance. There is an urgent need for better diagnostic and therapeutic strategies. Recently, protein post-translational modifications (PTMs) have gained significant attention for their role in the onset, progression, and treatment of ovarian cancer. PTMs (including phosphorylation, ubiquitination, methylation, ADP-ribosylation, and others) significantly influence tumor cell proliferation, metastasis, and drug resistance by modulating cellular signal transduction, DNA repair mechanisms, and metabolic processes. PARP inhibitors block the active site of PARP1 in BRCA-mutant ovarian cancer, disrupting ADP-ribosylation, inducing apoptosis in cancer cells, and extending progression-free survival. However, the emergence of drug resistance, such as BRCA reversal mutations, and the insufficient specificity of targets remain significant limitations to therapeutic efficacy. Strategies targeting other modification pathways, such as ubiquitination and methylation, provide promising options for expanding treatments. Combination therapies, like integrating PARP inhibitors with chemotherapy or immunotherapy, and precision medicine also show potential to overcome therapeutic challenges. This article systematically examines the pivotal role of PTMs in ovarian cancer pathogenesis, outlines therapeutic strategies and associated challenges in targeting PTMs, and offers a comprehensive overview with strategic guidance for future research.