Therapeutic Targeting of RAS Mutant Cancers

This Element reviews key aspects of RAS biochemistry that are directly relevant to understanding the newly available RAS inhibitors.

Edward C. Stites (Author), Kendra Paskvan (Author), Shumei Kato (Author)

9781009073646, Cambridge University Press

Paperback / softback, published 15 September 2022

75 pages
22.8 x 15.2 x 0.3 cm, 0.08 kg

The KRAS oncogene is believed to be the most common single nucleotide variant oncogene in human cancer. Historically, efforts to target KRAS and the other RAS GTPases have struggled. More recently, efforts have focused on identifying and exploiting features unique to specific oncogenic mutations. This has led to the first FDA approval for a RAS targeted therapy. This new agent is a covalent inhibitor that reacts with the cysteine residue created by a codon 12 glycine to cysteine (G12C) mutation within KRAS. Mutant-specific strategies may also exist for other KRAS single nucleotide variants, and recent studies provide examples and mechanisms.

Introduction
RAS Biology
Oncogenic RAS
RAS Targeting
Downstream Targeting
Upstream Targeting
Targeting Specific RAS Mutants
KRAS G12C Targeting
Direct Targeting of Other RAS Proteins
KRAS G12R Pancreatic Cancer
KRAS G13D Colorectal Cancer
Summary
References.

Subject Areas: Pharmacology [MMG], Pathology [MMF], Oncology [MJCL]