[Targeting the RAS signalling pathway in cancer]

Abstract

RAS proteins are among the first proteins to demonstrate a crucial implication in the cell cycle regulation. The RAS signalling pathway plays a key role in the regulation of cell cycle through the activation of numerous downstream pathways including the RAF/MEK/ERK, PI3K/AKT/mTOR, RAL and PKC pathways. These pathways are involved in gene transcription, regulation of cell survival and angiogenesis. As the RAS signalling pathway was shown to be altered in several cancers, molecularly targeted agents that trigger various components of this pathway have been evaluated in clinical practice. This paper first reviews the regulation processes of the RAS protein in cancer, as well as RAS downstream main signalling pathways. Therapeutic approaches to target RAS or some of its effectors are then detailed. Finally, the ability of RAS mutations to predict response to EGFR-targeting agents is discussed in the context of colorectal and lung cancers.