Department of Clinical Therapeutics, Alexandra Hospital, Medical School, 11528 Athens, Greece.
2nd Propaedeutic Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, "ATTIKON" University Hospital, Rimini 1, 12462 Chaidari, Greece.
Int J Mol Sci. 2020 Nov 22;21(22):8829. doi: 10.3390/ijms21228829.
ERCC1 is a key regulator of nucleotide excision repair (NER) pathway that repairs bulky DNA adducts, including intrastrand DNA adducts and interstrand crosslinks (ICLs). Overexpression of ERCC1 has been linked to increased DNA repair capacity and platinum resistance in solid tumors. Multiple single nucleotide polymorphisms (SNPs) have been detected in ERCC1 gene that may affect ERCC1 protein expression. Platinum-based treatment remains the cornerstone of urothelial cancer treatment. Given the expanding application of neoadjuvant and adjuvant chemotherapy in locally advanced bladder cancer, there is an emerging need for biomarkers that could distinguish potential responders to cisplatin treatment. Extensive research has been done regarding the prognostic and predictive role of ERCC1 gene expression and polymorphisms in bladder cancer. Moreover, novel compounds have been recently developed to target ERCC1 protein function in order to maximize sensitivity to cisplatin. We aim to review all the existing literature regarding the role of the ERCC1 gene in bladder cancer and address future perspectives for its clinical application.
ERCC1 是核苷酸切除修复 (NER) 途径的关键调节因子,可修复包括链内 DNA 加合物和链间交联 (ICLs) 在内的大体积 DNA 加合物。ERCC1 的过表达与实体瘤中 DNA 修复能力的增加和铂类耐药性有关。已经在 ERCC1 基因中检测到多个单核苷酸多态性 (SNP),这些 SNP 可能影响 ERCC1 蛋白的表达。铂类药物仍然是膀胱癌治疗的基石。鉴于新辅助和辅助化疗在局部晚期膀胱癌中的应用不断扩大,人们迫切需要能够区分顺铂治疗潜在反应者的生物标志物。已经对 ERCC1 基因表达和多态性在膀胱癌中的预后和预测作用进行了广泛的研究。此外,最近还开发了新型化合物来靶向 ERCC1 蛋白功能,以最大限度地提高对顺铂的敏感性。我们旨在回顾所有关于 ERCC1 基因在膀胱癌中的作用的现有文献,并探讨其临床应用的未来前景。