Drugging the undruggable proteins in cancer: A systems biology approach |
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| Institution: | 1. Donnelly Centre, University of Toronto, Ontario, Canada;2. Department of Molecular Genetics, University of Toronto, Ontario, Canada;3. Department of Biochemistry, University of Toronto, Ontario, Canada;4. Mediterranean Institute for Life Sciences, Split, Croatia;5. School of Medicine, University of Split, Croatia;1. Stanford Cardiovascular Institute, Stanford University, 265 Campus Drive G1120B, Stanford, CA 94304, USA;2. Department of Medicine, City of Hope Comprehensive Cancer Center, 1500 E Duarte Rd, Duarte, CA 91010, USA;3. Department of Medicine, Division of Cardiovascular Medicine, Stanford University;4. Department of Radiology, Stanford University, 265 Campus Drive G1120B, Stanford, CA 94304, USA;1. Department of Chemistry, Stanford University, Stanford, CA, USA;2. Stanford ChEM-H, Stanford University, Stanford, CA, USA;1. Department of Chemistry and Biochemistry, University of California Santa Cruz, 1156 High St., Santa Cruz, CA 95064, United States;2. Circle Pharma, Inc., 280 Utah Ave, Suite 100, South San Francisco, CA 94080, United States;3. Sage Therapeutics, 215 First Street, Suite 220, Cambridge, MA 02142, United States;1. Donnelly Centre, University of Toronto, Toronto, ON, Canada;2. Department of Biochemistry, University of Toronto, Toronto, ON, Canada;3. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada;4. Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada;5. Mediterranean Institute for Life Sciences (MedILS), Split, Croatia;6. School of Medicine, University of Split, Croatia;1. Division of Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, UK;2. Boehringer Ingelheim RCV GmbH & Co KG, Dr. Boehringer Gasse 5-11, A-1121, Vienna, Austria |
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| Abstract: | In recent years, the research community has, with comprehensive systems biology approaches and related technologies, gained insight into the vast complexity of numerous cancers. These approaches allow an in-depth exploration that cannot be achieved solely using conventional low-throughput methods, which do not closely mimic the natural cellular environment. In this review, we discuss recent integrative multiple omics approaches for understanding and modulating previously identified ‘undruggable’ targets such as members of the RAS family, MYC, TP53, and various E3 ligases and deubiquitinases. We describe how these technologies have revolutionized drug discovery by overcoming an array of biological and technological challenges and how, in the future, they will be pivotal in assessing cancer states in individual patients, allowing for the prediction and application of personalized disease treatments. |
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| Keywords: | Cancer research Undruggable oncogenes Difficult-to-drug proteome RAS MYC TP53 E3 ligases and deubiquitinases Systems Biology Omics High-throughput Drug discovery Precision medicine |
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