Small Molecule Inhibitors Targeting Key Proteins in the DNA Damage Response for Cancer Therapy

Lulu       Li; Alagamuthu    Karthick    Kumar; Zhigang       Hu; Zhigang       Guo
doi:10.2174/0929867327666200224102309
Abstract

DNA damage response (DDR) is a complicated interactional pathway. Defects that occur in subordinate pathways of the DDR pathway can lead to genomic instability and cancer susceptibility. Abnormal expression of some proteins in DDR, especially in the DNA repair pathway, are associated with the subsistence and resistance of cancer cells. Therefore, the development of small molecule inhibitors targeting the chief proteins in the DDR pathway is an effective strategy for cancer therapy. In this review, we summarize the development of small molecule inhibitors targeting chief proteins in the DDR pathway, particularly focusing on their implications for cancer therapy. We present the action mode of DDR molecule inhibitors in preclinical studies and clinical cancer therapy, including monotherapy and combination therapy with chemotherapeutic drugs or checkpoint suppression therapy.
Keywords: DNA damage response (DDR), DNA repair, small molecule inhibitor, cancer therapy, monotherapy, combination therapy, synthetic lethal (SL), drug repurposing.
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DOI https://dx.doi.org/10.2174/0929867327666200224102309	Print ISSN 0929-8673
Publisher Name Bentham Science Publisher	Online ISSN 1875-533X
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