NON-THEMATIC REVIEW DNA repair pathways and their implication in cancer treatment Athanasios G. Pallis & Michalis V. Karamouzis Published online: 7 September 2010 # Springer Science+Business Media, LLC 2010 Abstract Many cytotoxic agents used in cancer treatment exert their effects through their ability to directly or indirectly damage DNA and thus resulting in cell death. Major types of DNA damage induced by anticancer treatment include strand breaks (double or single strand), crosslinks (inter-strand, intra-strand, DNA–protein crosslinks), and interference with nucleotide metabolism and DNA synthesis. On the other hand, cancer cells activate various DNA repair pathways and repair DNA damages induced by cytotoxic drugs. The purpose of the current review is to present the major types of DNA damage induced by cytotoxic agents, DNA repair pathways, and their role as predictive agents, as well as evaluate the future perspectives of the novel DNA repair pathways inhibitors in cancer therapeutics. Keywords DNA repair pathways . Cancer treatment . Cytotoxic drugs 1 Introduction Many antineoplastic drugs currently used in cancer treatment express their cytotoxic effects through their ability to directly or indirectly damage DNA and thus resulting in cell death [1]. A very important mechanism that results in development of resistance to these agents is that cancer cells activate various DNA repair pathways and repair the DNA damages induced by cytotoxic drugs [2]. Major types of DNA damage induced by anticancer treatment include strand breaks (double or single strand) [3, 4], crosslinks (inter-strand, intra-strand, and DNA–protein crosslinks) [5], and interference with nucleotide metabolism and DNA synthesis. On the other hand, the mechanisms used by cancer cells for DNA repair include the direct repair pathway, the base excision and the nucleotide excision repair pathways, the mismatch repair pathway, and the homologous recombination and the non-homologous end-joining pathway [6]. The expression of several elements of these repair pathways has been demonstrated to have a predictive value for response to different chemotherapeutic agents [7]. Furthermore, improvements in our understanding in the molecular biology of the cancer cell has led to the development of pharmacological agents that can inhibit certain DNA repair pathways, enhance the cytotoxicity of anticancer treatments, and reverse the therapeutic resistance associated with DNA repair pathways [8]. It is obvious that these agents represent a promising opportunity to achieve better therapeutic efficacy. The purpose of this review is to present the major DNA repair pathways and their role as predictive markers. Furthermore, novel DNA repair pathways inhibitors under development in the clinical setting will be briefly presented. 2 DNA repair pathways 2.1 Direct repair pathway Cytotoxic and mutagenic methylated bases in DNA can be created by endogenous and environmental alkylating A. G. Pallis Department of Medical Oncology, University General Hospital of Heraklion, Heraklion, Greece M. V. Karamouzis (*) Department of Biological Chemistry, School of Medicine, University of Athens, Athens, Greece e-mail: karam@otenet.gr Cancer Metastasis Rev (2010) 29:677–685 DOI 10.1007/s10555-010-9258-8