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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
de Almeida, Larissa Costa [1] ; Calil, Felipe Antunes [2] ; Machado-Neto, Joao Agostinho [1] ; Costa-Lotufo, Leticia Veras [1]
Total Authors: 4
Affiliation:
[1] Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, Ave Prof Lineu Prestes 1524, BR-05508900 Sao Paulo - Brazil
[2] Univ Calif San Diego, Sch Med, Ludwig Inst Canc Res, La Jolla, CA 92093 - USA
Total Affiliations: 2
Document type: Review article
Source: CANCER GENETICS; v. 252, p. 6-24, APR 2021.
Web of Science Citations: 6
Abstract

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. (AU)

FAPESP's process: 19/23864-7 - Comprehensive analysis of genomic data for identification and validation of novel therapeutic targets involved in cellular cytoskeleton regulation in acute Leukemia
Grantee:João Agostinho Machado Neto
Support Opportunities: Regular Research Grants