Base Excision Repair: Contribution to Tumorigenesis and Target in Anticancer Treatment Paradigms

Abstract

Cancer treatments often lose their effectiveness due to the development of multiple drug resistance. Thus, identification of key proteins involved in the tumorigenic process and the survival mechanism(s), coupled with the design of novel therapeutic compounds (such as small molecule inhibitors), are essential steps towards the establishment of improved anticancer treatment strategies. DNA repair pathways and their proteins have been exposed as potential targets for combinatorial anticancer therapies that involve DNA-interactive cytotoxins, such as alkylating agents, because of their central role in providing resistance against DNA damage. In addition, an understanding of the tumor-specific genetics and associated DNA repair capacity has allowed research scientists and clinicians to begin to devise more targeted treatment strategies based on the concept of synthetic lethality. In this review, the repair mechanisms, as well as the links to cancer progression and treatment, of three key proteins that function in the base excision repair pathway, i.e. APE1, POLβ, and FEN1, are discussed.

Emerging Roles of the Nucleolus in Regulating the DNA Damage Response: The Noncanonical DNA Repair Enzyme APE1/Ref-1 as a Paradigmatical Example

“…BER proteins have been broadly explored as targets for cancer therapy (67); in particular, current approaches to cancer treatment report more effective results when specific DNA repair inhibitors are used in combination with DNA damaging drugs. The foremost rationale of the combined therapy is that impairment of BER enzymes is likely to sensitize cancer cells to chemotherapeutic agents.…”

Identification and Quantification of DNA Repair Protein Apurinic/Apyrimidinic Endonuclease 1 (APE1) in Human Cells by Liquid Chromatography/Isotope-Dilution Tandem Mass Spectrometry

“…Mounting evidence points to the predictive and prognostic value of APE1 expression and subcellular localization in human cancers [24], [25]. For instance, strict APE1 nuclear localization typically associates with a good prognosis, whereas combined cytoplasmic and nuclear localization correlates with poor survival.…”

Roles of GST-π and polβ Genes in Chemoresistance of Esophageal Carcinoma Cells

“…Recent research has revealed the involvement of polβ in chemoresistance in tumor cells. For example, upregulated polβ expression is associated with resistance to cisplatin in tumor cells (Li et al, 2007;Illuzzi and Wilson, 2012). Previous research by our group further disclosed that GST-π and polβ genes are likely to play an important role in function in MDR in EC9706/ cDDP cells.…”