DNA Double Strand Breaks Repair Inhibitors: Relevance as Potential New Anticancer Therapeutics

Author(s): Paulina Kopa, Anna Macieja, Grzegorz Galita, Zbigniew J. Witczak*, Tomasz Poplawski

Journal Name: Current Medicinal Chemistry

Volume 26 , Issue 8 , 2019

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Abstract:

DNA double-strand breaks are considered one of the most lethal forms of DNA damage. Many effective anticancer therapeutic approaches used chemical and physical methods to generate DNA double-strand breaks in the cancer cells. They include: IR and drugs which mimetic its action, topoisomerase poisons, some alkylating agents or drugs which affected DNA replication process. On the other hand, cancer cells are mostly characterized by highly effective systems of DNA damage repair. There are two main DNA repair pathways used to fix double-strand breaks: NHEJ and HRR. Their activity leads to a decreased effect of chemotherapy. Targeting directly or indirectly the DNA double-strand breaks response by inhibitors seems to be an exciting option for anticancer therapy and is a part of novel trends that arise after the clinical success of PARP inhibitors. These trends will provide great opportunities for the development of DNA repair inhibitors as new potential anticancer drugs. The main objective of this article is to address these new promising advances.

Keywords: Double-strand breaks repair, DNA double-strand breaks, homologous recombination, non-homologous end joining, anti-cancer therapy, inhibitors.

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VOLUME: 26
ISSUE: 8
Year: 2019
Page: [1483 - 1493]
Pages: 11
DOI: 10.2174/0929867325666180214113154
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