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Targeting the cancer kinome through polypharmacology

Nature Reviews Cancer volume 10, pages 130–137 (2010)Cite this article

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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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Figure 1: Resistance to kinase inhibitors.
Figure 2: Degrees of oncogene addiction.
Figure 3: Strategies for multi-targeted kinase inhibition.
Figure 4: Selectivity profiling of kinase inhibitors.
Figure 5: Polypharmacology in the protein kinome.

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Acknowledgements

This work was partly supported by the US National Institutes of Health grants DK083531 (Z.A.K.) and EB001987 (K.M.S.).

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Authors and Affiliations

  1. Zachary A. Knight is at The Rockefeller University, New York, New York 10065, USA.,

    Zachary A. Knight

  2. Henry Lin and Kevan M. Shokat are at the Howard Hughes Medical Institute and Department of Cellular and Molecular Pharmacology, University of California, San Francisco, California 94158, USA.,

    Henry Lin & Kevan M. Shokat

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  1. Zachary A. Knight
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Correspondence to Zachary A. Knight or Kevan M. Shokat.

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DATABASES

National Cancer Institute Drug Dictionary

bevacizumab

cetuximab

dasatinib

erlotinib

flavopiridol

imatinib

irinotecan

lapatinib

nilotinib

rapamycin

sorafenib

trastuzumab

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Knight, Z., Lin, H. & Shokat, K. Targeting the cancer kinome through polypharmacology. Nat Rev Cancer 10, 130–137 (2010). https://doi.org/10.1038/nrc2787

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