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Targeting non-oncogene addiction for cancer therapy

Authors
Chang, H.R.Jung, E.Cho, S.Jeon, Y.-J.Kim, Y.
Issue Date
Feb-2021
Publisher
MDPI AG
Keywords
Cancer therapy; DNA damage response; DNA repair; Non-oncogene addiction
Citation
Biomolecules, v.11, no.2, pp.1 - 21
Journal Title
Biomolecules
Volume
11
Number
2
Start Page
1
End Page
21
URI
https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/146830
DOI
10.3390/biom11020129
ISSN
2218-273X
Abstract
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. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
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