Journal
CANCER GENETICS
Volume 252, Issue -, Pages 6-24Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cancergen.2020.12.002
Keywords
Cancer; DNA damage; DNA repair; Chemotherapy; Carcinogenesis
Categories
Funding
- Sao Paulo Research Foundation (FAPESP) [2017/176 48-4, 2019/23864-7, 2015/171776]
- National Institute of Science and Technology - INCT BioNat (CNPQ) [465637/2014-0]
- National Institute of Science and Technology - INCT BioNat (FAPESP, Brazil) [2014/509260]
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior - Brasil (CAPES) [001]
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Cancer genome instability is caused by various defects in DNA repair machinery, making cancer cells more vulnerable to DNA targeting agents. The interaction between DNA repair deficiency and increased effects of DNA targeting agents emphasizes the importance of double-strand break (DSB) repair. Despite limitations, DNA-targeting drugs play a crucial role in cancer therapy when combined with targeted therapy and immunotherapy.
Cancer genome instability arises from diverse defects in DNA-repair machinery, which make cancer cells more susceptible to DNA targeting agents. The interrelation between DNA repair deficiency and the increased effect of DNA targeting agents highlights the double-strand break (DSB) repair, which comprises the homologous recombination (HR) and non-homologous end joining (NHEJ) pathways. The DNA targeting agents are classified into two major groups: non-covalent DNA binding agents and covalent DNA-reactive agents. Although these agents have well-known limitations, such as resistance and secondary carcinogenesis risk, they are extremely important in today's real-life cancer therapy in combination with targeted therapy and immunotherapy. Indeed, DNA targeting drugs are promising therapeutics with a precise application through the background of cancer-specific DNA repair failure. In the current review, the mechanisms of action of diversified DNA-targeting agents, as well as the modulation of DNA repair pathways to increase the DNA-damaging drugs efficacy are presented. Finally, DNA-targeting-based therapies are discussed considering risks, resistance and its uses in the medicine precision era. (C) 2020 Elsevier Inc. All rights reserved.
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