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Ras proteins are guanine nucleotide-binding proteins that are central to the control of normal and transformed cell growth and that are mutated in approximately 30% of human cancers. Binding of ligands to various growth factor receptors activates Ras and subsequently a plethora of downstream effectors including the Raf-1/mitogen-activated protein kinase pathway. For effective ras functioning and for transformation, Ras proteins must undergo post-translational modifications that facilitate their attachment to the plasma membrane. Farnesylation, catalysed by farnesyl protein transferase (FPT), is the first and the most important of these modifications; inhibition of which ablates ras activity, resulting in significant anti-proliferative effect in vitro and in human cancer xenograft models. FPT inhibitors are being assessed in a range of phase I and phase II trials, which incorporate both pharmacokinetic and dynamic end-points. In addition, ras mutations can also generate neo-epitopes for cytotoxic and helper T-cell recognition, rendering ras-mutated tumours a potential target for immunotherapy. Though their clinical evaluation is still in infancy, these two modes of ras targeting represent rational therapeutic strategies that can undergo mechanistic evaluation in the clinic.

Original publication




Journal article


Crit Rev Oncol Hematol

Publication Date





109 - 120


Alkyl and Aryl Transferases, Antineoplastic Agents, Enzyme Inhibitors, Humans, Immunotherapy, Neoplasms, Protein Processing, Post-Translational, ras Proteins