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RAS-targeted therapies

RAS, a small GTPase, is one of the most frequently altered proteins in cancer. Decades of research into the mechanisms through which RAS is activated and affects downstream signalling have elucidated much of the basic biology that underpins this key molecule. Despite this insight and multiple attempts to create RAS inhibitors, no RAS-targeted therapeutic is currently approved for widespread clinical use.

That is set to change. Therapies that target versions of RAS that have a G to C mutation in codon 12, the most frequent RAS-activating mutation in non-small cell lung cancer, are in late-stage clinical development, and at least one could be approved by the end of 2021. Such molecules have reignited the field of RAS therapeutics; numerous companies are developing other potential RAS-targeting therapies, or are exploring combinations of therapies that will prevent RAS’s oncogenic effects.

This poster from Nature Reviews Drug Discovery illustrates some of the key developments in our understanding of RAS, including the RAS mutational spectrum and the signalling pathways that pass through RAS. Structures of RAS, alone or bound to inhibitors or tool molecules, have highlighted regions of RAS that could be amenable to inhibition. Some of these regions are being targeted by the therapies that are in development. These therapies could substantially improve the treatment of certain types of cancer, and are a major step towards personalized medicines for cancer.

This poster is freely available online thanks to support from Reaction Biology.

The poster has been peer reviewed and, as always, Springer Nature retains sole responsibility for all editorial content.

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Correspondence to Shiva Malek.

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Moore, A.R., Rosenberg, S.C., McCormick, F. et al. RAS-targeted therapies. Nat Rev Drug Discov (2021).

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