Journal
BIOMOLECULES
Volume 11, Issue 2, Pages -Publisher
MDPI
DOI: 10.3390/biom11020129
Keywords
non-oncogene addiction; DNA damage response; DNA repair; cancer therapy
Categories
Funding
- National Research Foundation (NRF) - Ministry of Science, ICT and Future Planning of the Korean government [NRF-2014M3C9A2064688, NRF-2019R1A2C2089746, NRF-2016R1A5A1011974, NRF-2018R1D1A1B07045893]
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This review highlights the importance of DNA replication, DDR, DNA repair, and cell cycle regulation in targeted cancer therapies, with a focus on potential therapeutic targets such as TONSL. The utilization of synthetic lethality for developing novel inhibitors targeting non-oncogene addiction in cancer therapy is also discussed in depth.
While Next-Generation Sequencing (NGS) and technological advances have been useful in identifying genetic profiles of tumorigenesis, novel target proteins and various clinical biomarkers, cancer continues to be a major global health threat. DNA replication, DNA damage response (DDR) and repair, and cell cycle regulation continue to be essential systems in targeted cancer therapies. Although many genes involved in DDR are known to be tumor suppressor genes, cancer cells are often dependent and addicted to these genes, making them excellent therapeutic targets. In this review, genes implicated in DNA replication, DDR, DNA repair, cell cycle regulation are discussed with reference to peptide or small molecule inhibitors which may prove therapeutic in cancer patients. Additionally, the potential of utilizing novel synthetic lethal genes in these pathways is examined, providing possible new targets for future therapeutics. Specifically, we evaluate the potential of TONSL as a novel gene for targeted therapy. Although it is a scaffold protein with no known enzymatic activity, the strategy used for developing PCNA inhibitors can also be utilized to target TONSL. This review summarizes current knowledge on non-oncogene addiction, and the utilization of synthetic lethality for developing novel inhibitors targeting non-oncogenic addiction for cancer therapy.
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