Recent Advances in Therapeutic Application of DNA Damage Response Inhibitors
against Cancer

Stina    George    Fernandes; Prachi       Shah; Ekta       Khattar
doi:10.2174/1871520621666210608105735
Abstract

DNA’s integrity is continuously challenged by intrinsic cellular processes and environmental agents. To overcome this genomic damage, cells have developed multiple signalling pathways collectively named as DNA Damage Response (DDR) and composed of three components: (i) sensor proteins, which detect DNA damage, (ii) mediators that relay the signal downstream and recruit the repair machinery and (iii) the repair proteins, which restore the damaged DNA. A flawed DDR and failure to repair the damage lead to the accumulation of genetic lesions and increased genomic instability, which is recognized as a hallmark of cancer. Cancer cells tend to harbor increased mutations in DDR genes and often have fewer DDR pathways than normal cells. This makes cancer cells more dependent on particular DDR pathways and thus become more susceptible to compounds inhibiting those pathways compared to normal cells, which have all the DDR pathways intact. Understanding the roles of different DDR proteins in the DNA damage response and repair pathways and the identification of their structures have paved the way for development of their inhibitors as targeted cancer therapy. In this review, we describe the major participants of various DDR pathways, their significance in carcinogenesis and focus on the inhibitors developed against several key DDR proteins.
Keywords: DNA damage response, double strand breaks, checkpoint inhibitors, synthetic lethality, targeted cancer therapy, response inhibitors.
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Graphical Abstract

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DOI https://dx.doi.org/10.2174/1871520621666210608105735	Print ISSN 1871-5206
Publisher Name Bentham Science Publisher	Online ISSN 1875-5992
Anti-Cancer Agents in Medicinal Chemistry

Recent Advances in Therapeutic Application of DNA Damage Response Inhibitors against Cancer

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