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Small molecule combats cancer-causing KRAS protein at last

A molecule has now been characterized that acts to inhibit a cancer-causing form of KRAS protein and stimulate the immune system. The inhibitor is one of the first of its kind to show anticancer activity in the clinic.
  1. Roy S. Herbst

    1. Roy S. Herbst is in the Department of Medicine, Yale School of Medicine, Yale Cancer Center, New Haven, Connecticut 06520, USA.

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  2. Joseph Schlessinger

    1. Joseph Schlessinger is in the Department of Pharmacology, Yale School of Medicine.

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Mutations in the gene KRAS are the most frequent drivers of tumour development across the spectrum of human cancers1. Despite this prevalence, mutant KRAS protein has remained an intractable therapeutic target. Writing in Nature, Canon et al.2 describe a small molecule that binds one form of mutant KRAS with high specificity and sensitivity, inhibiting the protein. The authors use animal models to analyse how the inhibitor works, and show that it can shrink tumours in patients. This is among the first evidence of a clinical response to a specific KRAS inhibitor.

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Nature 575, 294-295 (2019)

doi: https://doi.org/10.1038/d41586-019-03242-8

References

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Competing Interests

R.S.H. has received honoraria from the following:

Consulting: Abbvie Pharmaceuticals, ARMO Biosciences, AstraZeneca, Biodesix, Bolt Biotherapeutics, Bristol-Myers Squibb, Eli Lilly and Company, EMD Serrano, Genentech/Roche, Genmab, Halozyme, Heat Biologics, IMAB Biopharma, Immunocore, Infinity Pharmaceuticals, Loxo Oncology, Merck and Company, Midas Health Analytics, Nektar, Neon Therapeutics, NextCure, Novartis, Pfizer, Sanofi, Seattle Genetics, Shire PLC, Spectrum Pharmaceuticals, Symphogen, Takeda, Tesaro, Tocagen.

Research support: AstraZeneca, Eli Lilly and Company, Merck and Company.

He is a member of the board of directors (non-executive/ independent) for Junshi Pharmaceuticals.

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