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Drugging the 'undruggable' cancer targets

Nature Reviews Cancer volume 17, pages 502–508 (2017)Cite this article

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Abstract

The term 'undruggable' was coined to describe proteins that could not be targeted pharmacologically. However, progress is being made to 'drug' many of these targets, and therefore more appropriate terms might be 'difficult to drug' or 'yet to be drugged'. Many desirable targets in cancer fall into this category, including the RAS and MYC oncogenes, and pharmacologically targeting these intractable proteins is now a key challenge in cancer research that requires innovation and the development of new technologies. In this Viewpoint article, we asked four scientists working in this field for their opinions on the most crucial advances, as well as the challenges and what the future holds for this important area of research.

What would you say are the key so-called undruggable targets in cancer (and why)?

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Acknowledgements

K.M.S. would like to thank J. Taunton for pointing out the example of GBT440. L.S. acknowledges funding from the European Research Council (CoG Grant #617473), the Instituto de Salud Carlos III (FIS Grant #PI13/01705 and #PI16/01224), the BBVA Foundation and the FERO Foundation.

Author information

Author notes

  1. Chi V. Dang

    Present address: Present addresses: Ludwig Institute for Cancer Research, New York, New York 10017, USA, and The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.,

  2. dangvchi@upenn.edu

  3. dangc77@gmail.com

Authors and Affiliations

  1. Abramson Cancer Center, University of Pennsylvania, Philadelphia, 19104, Pennsylvania, USA

    Chi V. Dang

  2. Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, 10029, New York, USA

    E. Premkumar Reddy

  3. Department of Cellular and Molecular Pharmacology, University of California, San Francisco & Howard Hughes Medical Institute, San Francisco, 94158, California, USA

    Kevan M. Shokat

  4. Vall d'Hebron Institute of Oncology (VHIO), Cellex Centre, Barcelona, 08035

    Laura Soucek & Laura Soucek

  5. Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, 08010

    Laura Soucek

  6. Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, Bellaterra, 08193, Spain

    Laura Soucek

Authors
  1. Chi V. Dang
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  2. E. Premkumar Reddy
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  3. Kevan M. Shokat
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  4. Laura Soucek
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Corresponding authors

Correspondence to Chi V. Dang, E. Premkumar Reddy, Kevan M. Shokat or Laura Soucek.

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Competing interests

C.V.D. declares no competing interests. E.P.R. is the scientific founder, Board member and paid consultant of Onconova Therapeutics, Inc., which is developing rigosertib for cancer therapy. K.M.S. is an inventor on patents related to KRAS-G12C-targeting drugs licensed to Araxes Pharma. He is also a shareholder and consultant to Araxes Pharma. L.S. is founder and shareholder of Peptomyc S.L.

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Dang, C., Reddy, E., Shokat, K. et al. Drugging the 'undruggable' cancer targets. Nat Rev Cancer 17, 502–508 (2017). https://doi.org/10.1038/nrc.2017.36

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