Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Hidden Targets in RAF Signalling Pathways to Block Oncogenic RAS Signalling

Version 1 : Received: 21 March 2021 / Approved: 22 March 2021 / Online: 22 March 2021 (10:29:37 CET)

A peer-reviewed article of this Preprint also exists.

Nolan, A.A.; Aboud, N.K.; Kolch, W.; Matallanas, D. Hidden Targets in RAF Signalling Pathways to Block Oncogenic RAS Signalling. Genes 2021, 12, 553. Nolan, A.A.; Aboud, N.K.; Kolch, W.; Matallanas, D. Hidden Targets in RAF Signalling Pathways to Block Oncogenic RAS Signalling. Genes 2021, 12, 553.

Journal reference: Genes 2021, 12, 553
DOI: 10.3390/genes12040553

Abstract

Abstract: Oncogenic RAS mutations drive more than half of human cancers, and RAS inhibition is the holy grail of oncology. Thirty years of relentless efforts and harsh disappointments have taught us about the intricacies of oncogenic RAS signalling that allow us to now get a pharmacological grip on this elusive protein. The inhibition of effector pathways, such as the RAF-MEK-ERK pathway, has largely proven disappointing. So far, most of these efforts were aimed at blocking the activation of ERK. Here, we discuss RAF dependent pathways that are regulated through RAF functions independent of catalytic activity and their potential role as targets to block oncogenic RAS signalling. We focus on the now well documented roles of RAF kinase independent functions in apoptosis, cell cycle progression and cell migration.

Subject Areas

RAF kinase independent; RAS; MST2; ASK; PLK; RHO-α; apoptosis; cell cycle; cancer therapy

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