The Role of ERCC۱ and XRCC۱ in Cisplatin Resistance: Mechanisms and Clinical Implications

Cisplatin remains a cornerstone of treatment for various solid tumors; however, the emergence of intrinsic and acquired resistance significantly limits its clinical efficacy. Among the diverse mechanisms contributing to cisplatin resistance, enhanced DNA repair capacity particularly through the nucleotide excision repair (NER) and base excision repair (BER) pathways plays a central role. ERCC۱, a key component of the NER pathway, forms a functional endonuclease complex with XPF that is essential for the excision of cisplatin‑induced DNA adducts. Elevated ERCC۱ expression or specific polymorphisms can increase DNA repair efficiency, thereby reducing treatment sensitivity. Similarly, XRCC۱ acts as a scaffold protein within the BER pathway, coordinating critical repair enzymes involved in resolving oxidative and single‑strand DNA lesions generated during cisplatin exposure. Altered XRCC۱ expression or genetic variants such as Arg۳۹۹Gln influence DNA repair capacity and have been associated with variable therapeutic responses. Evidence indicates that concurrent upregulation of ERCC۱ and XRCC۱ contributes to multifactorial resistance, poorer prognosis, and reduced survival across multiple cancer types. Understanding the mechanistic roles and clinical implications of these genes is essential for developing predictive biomarkers and designing targeted therapeutic strategies. Integrating ERCC۱ and XRCC۱ profiling into precision oncology may enhance treatment stratification and improve outcomes for patients receiving platinum‑based chemotherapy.

کلیدواژه ها:

ERCC ، XRCC ، Cisplatin resistance ، DNA repair ، polymorphism