Cited by 714Cancer Mechanisms and TherapyProtein Kinase Regulation and GTPase SignalingComputational Drug Discovery Methods

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Targeting the cancer kinome through polypharmacology

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Knight, Zachary A., Lin, Henry, Shokat, Kevan M.·2010·Nature reviews. Cancer

DOI 10.1038/nrc2787PMC PMC2880454

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Abstract

Kinase inhibitors are the largest class of new cancer drugs. However, it is already apparent that most tumours can escape from the inhibition of any single kinase. If it is necessary to inhibit multiple kinases, how do we choose which ones? In this Opinion article, we discuss some of the strategies that are currently being used to identify new therapeutic combinations of kinase targets.

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Authors: Knight, Z. A., Lin, H., & Shokat, K. M.
Affiliations: Rockefeller University (US)
Howard Hughes Medical Institute (US)
Corresponding author: Knight, Zachary A.
Shokat, Kevan M.
ORCID: Knight, Zachary A.
Shokat, Kevan M.
Venue: Nature reviews. Cancer
Publisher: Springer Science and Business Media LLC
Published: 2010-02
Volume: 10
Issue: 2
Pages: 130-137
ISSN: 1474-175X (ISSN-L)
1474-1768
DOI: 10.1038/nrc2787
PMC: PMC2880454
OpenAlex: W2022609682
Cited by: 674
References: 104
Citations by year: 2026: 17 · 2025: 20 · 2024: 21 · 2023: 22 · 2022: 24 · 2021: 29 · 2020: 47 · 2019: 34 · 2018: 45 · 2017: 51 · 2016: 43 · 2015: 48 · 2014: 72 · 2013: 70 · 2012: 43
FWCI: 8.19
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Nature reviews. Cancer (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: Howard Hughes Medical Institute
National Institutes of Health (5r01eb001987-15)
National Institute of Diabetes and Digestive and Kidney Diseases (R00DK083531, K99DK083531)
National Institute of Biomedical Imaging and Bioengineering (R01-EB001987)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Mechanisms and Therapy
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Drug Discovery › Computational Drug Discovery Methods
Keywords: kinase inhibitors, polypharmacology, combination therapy, drug resistance, anticancer drug development
MeSH terms: Antineoplastic Agents, Antineoplastic Combined Chemotherapy Protocols, Humans, Mutation, Neoplasms, Protein Kinases, Technology, Pharmaceutical, Drug Delivery Systems, Drug Resistance, Neoplasm, RNA, Small Interfering, Protein Kinase Inhibitors, Drug Discovery

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Targeting the cancer kinome through polypharmacology

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