Therapeutic modulation of k-ras signaling in colorectal cancer

Abstract

KRAS has an important role in colorectal carcinogenesis and mutant KRAS leads to a permanently activated k-ras protein. To exert its biological activity, k-ras requires post-translational modification by prenylation. K-ras modulation has become a promising concept for new therapies, mostly by interference with the mevalonate pathway and subsequently by the prenylation of k-ras. Clinical data of agents interfering with the mevalonate pathway and the prenylation of ras are summarized and suggest that these agents might be effective when administered in combination with anticancer drugs that target k-ras. Here, we discuss the novel concept that modulation of k-ras might potentiate EGFR therapy by altering the KRAS phenotype.