DNA repair endonuclease ERCC1-XPF as a novel therapeutic target to overcome chemoresistance in cancer therapy

Abstract

The ERCC1–XPF complex is a structure-specific endonuclease essential for the repair of DNA damage by the nucleotide excision repair pathway. It is also involved in other key cellular processes, including DNA interstrand crosslink (ICL) repair and DNA double-strand break (DSB) repair. New evidence has recently emerged, increasing our understanding of its requirement in these additional roles. In this review, we focus on the protein–protein and protein–DNA interactions made by the ERCC1 and XPF proteins and discuss how these coordinate ERCC1–XPF in its various roles. In a number of different cancers, high expression of ERCC1 has been linked to a poor response to platinum-based chemotherapy. We discuss prospects for the development of DNA repair inhibitors that target the activity, stability or protein interactions of the ERCC1–XPF complex as a novel therapeutic strategy to overcome chemoresistance.

The prognostic and predictive value of excision repair cross-complementation group 1 (ERCC1) protein in 1288 patients with head and neck squamous cell carcinoma treated with platinum-based therapy: a meta-analysis

“…In the DSB repair the ERCC1-XPF removes non-homologous 3' single-strands flaps at broken ends before they are rejoined. The ERCC1-XPF incises both sides of interstrand cross-links (34). On the other hand, platinum based chemotherapy and radiotherapy which are basics of the treatment of HNSCC patients exert their cytotoxic effect through formation of DNA damages.…”

High excision repair cross-complementation group 1 expression is associated with favorable prognostic factors in breast cancer

“…The NER pathway requires a number of factors. Among these factors, ERCC1 serves an essential role for the incision step and completion of the NER pathway (11). ERCC1 bind to XPF and forms the ERCC1-XPF complex (10,11).…”

“…Among these factors, ERCC1 serves an essential role for the incision step and completion of the NER pathway (11). ERCC1 bind to XPF and forms the ERCC1-XPF complex (10,11). The ERCC1-XPF complex is important as a structure-specific endonuclease in the NER pathway (11).…”

“…ERCC1 bind to XPF and forms the ERCC1-XPF complex (10,11). The ERCC1-XPF complex is important as a structure-specific endonuclease in the NER pathway (11). Therefore, certain studies have reported that the ERCC1-XPF complex can be an important factor for repairing the DNA damage induced by chemotherapeutic agents, including cisplatin; thus, the expression of ERCC1 has been considered as a predictive factor for resistance to platinum-based chemotherapy (10,11).…”

“…Therefore, chemotherapy with a platinum-based agent remains in use as a common treatment of choice for TNBC (9). Excision repair cross-complementation group 1 (ERCC1)-xeroderma pigmentosum complementation group F (XPF) complex repairs DNA damaged by anticancer agents; studies have reported that ERCC1 expression is an important factor in determining the poor response of chemotherapy (10,11). Certain studies have also reported that the expression of ERCC1 in TNBC may be a predictive factor of a poor response to platinum-based chemotherapy (12,13).…”