DNA damaging agents and DNA repair: From carcinogenesis to cancer therapy.

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. Copyright © 2020 Elsevier Inc. All rights reserved.

Citation

Larissa Costa de Almeida, Felipe Antunes Calil, João Agostinho Machado-Neto, Leticia Veras Costa-Lotufo. DNA damaging agents and DNA repair: From carcinogenesis to cancer therapy. Cancer genetics. 2021 Apr;252-253:6-24

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PMID: 33340831

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