Targeting base excision repair to improve cancer therapies

Abstract

Most commonly used cancer therapies, particularly ionizing radiation and certain classes of cytotoxic chemotherapies, cause cell death by damaging DNA. Base excision repair (BER) is the major system responsible for the removal of corrupt DNA bases and repair of DNA single strand breaks generated spontaneously and induced by exogenous DNA damaging factors such as certain cancer therapies. In this review, the physico-chemical properties of the proteins involved in BER are discussed with particular emphasis on molecular mechanisms coordinating repair processes. The aim of this review is to apply extensive knowledge that currently exists regarding the biochemical mechanisms involved in human BER to the molecular biology of current therapies for cancer. It is anticipated that the application of this knowledge will translate into the development of novel effective therapies for improving existing treatments such as radiation therapy and oxaliplatin chemotherapy.2

GSTP1, ERCC1 and ERCC2 Polymorphisms, Expression and Clinical Outcome of Oxaliplatin-based Adjuvant Chemotherapy in Colorectal Cancer in Chinese Population

“…The nucleotide excision repair activity have been shown to influence platinumbased chemotherapy (Sharma et al, 2007;Martin et al, 2008). The objective of our study was to evaluate the polymorphisms in GSTP1, ERCC1 Asn118Asn and ERCC2 Lys751Gln predict the survival of colorectal cancer patients receiving 5-FU/oxaliplatin chemotherapy.…”

DNA repair pathways and their implication in cancer treatment

“…1) [18,19]. Base excision repair (BER) also plays an important role in the repair of DNA single-strand breaks (SSBs) generated spontaneously or induced by exogenous DNA-damaging factors such as cytotoxic anticancer agents.…”

Knock out of DNA Polymerase Beta Gene Enhance Sensitivity to Adriamycin

“…Drug resistance is a critical component of chemotherapy failure in the clinical treatment of tumor. Numerous mechanisms were thought to explain drug resistance including drug uptake and secretion, drug activation and inactivation, anti-apoptotic and DNA damage repair [12]. A mass of anticancer drugs could induce DNA strand breaks, DNA adducts as well as crosslink, thus efficient DNA damage repair will contribute to intrinsic anticancer drug resistance and influence the outcome of therapy [13].…”