Advances in Cancer Research, volume 153 provides a timely review of the biology, biochemistry, and current approaches to therapeutically target the RAS oncoprotein, the most frequently mutated oncogene family in human cancers. 2021 saw the approval of the first direct RAS inhibitor (sotorasib) for use in treating non-small cell lung cancers harboring KRAS(G12C) mutations. The successful approval and use of this drug highlights that the once "undruggable� RAS is indeed pharmacologically tractable. This volume provides an overview of efforts to develop additional approaches to therapeutically target oncogenic RAS. In addition, the reader will find excellent reviews on the history and research efforts to understand the biochemistry and oncogenic activity of RAS in human cancers.
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Table of Contents
1. A brief history of RAS and the RAS InitiativeFrank McCormick
2. Not all RAS mutations are equal: A detailed review of the functional diversity of RAS hot spot mutations
Rachel A. Burge and G. Aaron Hobbs
3. Drug targeting opportunities en route to Ras nanoclusters
Karolina Pavic, Rohan Chippalkatti, and Daniel Abankwa
4. Targeting the ERK mitogen-activated protein kinase cascade for the treatment of KRAS-mutant pancreatic cancer
J. Nathaniel Diehl, Priya S. Hibshman, Irem Ozkan-Dagliyan, Craig M. Goodwin, Sarah V. Howard, Adrienne D. Cox, and Channing J. Der
5. Pan-RAS inhibitors: Hitting multiple RAS isozymes with one stone
Alexander B. Coley, Antonio Ward, Adam B. Keeton, Xi Chen, Yulia Maxuitenko, Aishwarya Prakash, Feng Li, Jeremy B. Foote, Donald J. Buchsbaum, and Gary A. Piazza
6. Targeting RAS oncogenesis with SOS1 inhibitors
Roman Christian Hillig and Benjamin Bader
7. Inhibition of SHP2 as an approach to block RAS-driven cancers
Yu-Ting Chou and Trever G. Bivona
8. Targeting the "undruggable� RAS with biologics
Michael Whaby, Imran Khan, and John P. O'Bryan
9. Unraveling and targeting RAS-driven metabolic signaling for therapeutic gain
Jonathan M. DeLiberty, Ryan Robb, Claire E. Gates, and Kirsten L. Bryant
10. The RASopathies: Biology, genetics and therapeutic options
Jody Fromm Longo and Steven L. Carroll
