Abstract:

Epithelial ovarian cancer (EOC) is a lethal malignancy whose treatment failure and recurrence are mainly attributed to platinum-based chemotherapy resistance. Centrin 2 (CETN2), a highly conserved centrosome-associated protein and DNA repair protein, has been implicated in platinum resistance in EOC. This review systematically outlines the structural and functional features of CETN2, focusing on its pivotal role in the nucleotide excision repair (NER) pathway, which serves as the key mechanism for removing platinum-induced DNA crosslink damage. CETN2 may drive platinum resistance through multiple mechanisms, including stabilizing the NER damage recognition complex (XPC complex) to enhance DNA damage repair efficiency, disrupting centrosome homeostasis to affect genomic stability, and regulating cell-cycle checkpoints, thereby conferring a survival advantage to EOC cells under genotoxic stress. Furthermore, the critical interaction between CETN2 and XPC protein provides a potential target for developing small-molecule inhibitors, which may not only directly reverse platinum resistance but also synergize with poly (ADP-ribose) polymerase (PARP) inhibitors, offering new combinatorial therapeutic strategies for EOC patients with intact homologous recombination repair function. However, current evidence relies heavily on bioinformatic analyses and clinical correlation studies, with a lack of functional experimental validation. Future research should focus on in-depth molecular mechanism elucidation and targeted intervention strategies to clarify the clinical translational potential of CETN2 as a reversal target for platinum resistance in EOC.

Key words: Carcinoma, ovarian epithelial, Platinum compounds, Drug resistance, neoplasm, DNA Repair, Centrin 2