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Annual Review of Cancer Biology

Volume 8, 2024

RAS and SHOC2 Roles in RAF Activation and Therapeutic Considerations

  • Daniel A. Bonsor1 and Dhirendra K. Simanshu1
  • NCI RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA; email: [email protected]
  • Vol. 8:97-113 (Volume publication date June 2024)
  • First published as a Review in Advance on December 05, 2023
  • Copyright © 2024 by the author(s).
    This work is licensed under a Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See credit lines of images or other third-party material in this article for license information.

Abstract

Mutations in RAS proteins play a pivotal role in the development of human cancers, driving persistent RAF activation and deregulating the mitogen-activated protein kinase (MAPK) signaling pathway. While progress has been made in targeting specific oncogenic RAS proteins, effective drug-based therapies for most RAS mutations remain limited. Recent investigations into RAS–RAF complexes and the SHOC2–MRAS–PP1C holoenzyme complex have provided crucial insights into the structural and functional aspects of RAF activation within the MAPK signaling pathway. Moreover, these studies have also unveiled new blueprints for developing inhibitors, allowing us to think beyond the current RAS and MEK inhibitors. In this review, we explore the roles of RAS and SHOC2 in activating RAF and discuss potential therapeutic strategies to target these proteins. A comprehensive understanding of the molecular interactions involved in RAF activation and their therapeutic implications can potentially drive innovative approaches in combating RAS-/RAF-driven cancers.

Keyword(s): 14-3-3 dimer, MRAS, PP1C, RAF, RAS, SHOC2
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2024-06-12
2025-06-22
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RAS and SHOC2 Roles in RAF Activation and Therapeutic Considerations
Annual Review of Cancer Biology 8, 97 (2024); https://doi.org/10.1146/annurev-cancerbio-062822-030450
/content/journals/10.1146/annurev-cancerbio-062822-030450
/content/journals/10.1146/annurev-cancerbio-062822-030450
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