Clinical Perspectives of ERCC1 in Bladder Cancer

Abstract

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.

Targeting DNA Damage Response and Repair to Enhance Therapeutic Index in Cisplatin-Based Cancer Treatment

“…ERCC1 is one of the key regulatory proteins within the NER pathway that plays a significant role in the repair of DNA adducts and intrastrand crosslinks (ICLs) generated by cisplatin [ 79 ]. ERCC1 overexpression is found in many different types of cisplatin-resistant cancers, such as HNSCC, bladder, and lung cancers [ 19 , 80 , 81 ].…”

Association of ERCC1 rs11615 Polymorphism with the Risk of Cervical Cancer Especially in Chinese Populations: A Meta-Analysis

“…Various DNA repair mechanisms, such as NER, BER, mismatch repair, and recombination repair mechanisms, control DNA damage [39]. ERCC1 is a pivotal regulatory factor in the nucleotide excision repair (NERs) pathway [40], and genetic variations in this gene can affect DNA repair [41,42]. SNPs are a common type of heritable variation in humans, and rs11615 (C > T) is a familiar polymorphism of the ERCC1 gene.…”

Perspectives of ERCC1 in early-stage and advanced cervical cancer: From experiments to clinical applications

“…ERCC1 is one of the DNA repair genes ( 45 ). Its enzyme involves the nucleotide excision repair pathway that recognizes and eliminates cisplatin-associated DNA adducts ( 13 , 46 ). One proposed mechanism for ERCC1 in cancer development might be due to the aberrant expression of ERCC1 causing the dysfunction of DNA-repair capacity, leading to the accumulation of genetic damage, which might induce the emergence of an aggressive tumor phenotype ( 47 ).…”

“…Excision repair cross-complementation group 1 (ERCC1) (the DNA repair gene) is a gene associated with platinum sensitivity and has been proposed as a novel biomarker of cervical cancer over the years ( 11 , 12 ). ERCC1 gene is located on 19q13.2-q13.3, and encodes a 297 amino acid protein ( 13 , 14 ). The C-terminal domain of ERCC1 interacts with xeroderma pigmentosum group F (XPF), which forms a heterodimeric protein complex.…”