Targeting a family of proteins important for cancer development using intracellular macromolecules
Targeted protein degradation
Proteins of the RAS superfamily (called small GTPases) and the signalling pathways they activate are necessary for proper cell function. These proteins are found mutated and/or deregulated in many human cancers. Thus, they function abnormally and change the properties of the healthy cell towards cancerous properties (proliferation, resistance to death, migration, invasion). Therefore, it is clearly important to produce drugs that can combat these proteins. Only one drug is clinically available to target a specific mutation in KRAS, a member of the RAS superfamily, while many other members remain to be targeted. While efforts are being made to develop drugs that target this class of proteins, antibody fragments or antibody mimetics are used inside cells where they bind their target. In this review, we discuss the use of intracellular binding proteins to discover new ways to inhibit small GTPases and their signalling pathways and to better understand the biological mechanisms regulated by these proteins.
Collaborations, Acknowledgements and Related Patents
This work was carried out in team 10. N.B. is financed by the Fondation de France (n°00097692)
Discover the published article
Biochem Soc Trans. 2021 Oct 8;BST20201059. doi: 10.1042/BST20201059. Online ahead of print.
Targeting small GTPases and their downstream pathways with intracellular macromolecule binders to define alternative therapeutic strategies in cancer
Marie Sorbara, Nicolas Bery
Toulouse Cancer Research Center (Oncopole)
Toulouse – FR
+33 5 82 74 15 75
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