Therapeutic modulation of k-ras signaling in colorectal cancer.
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.
Krens
Lisanne L
LL
Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands.
Baas
Jara M
JM
Gelderblom
Hans
H
Guchelaar
Henk-Jan
HJ
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D016283:Proto-Oncogene Proteins p21(ras); D015398:Signal Transduction / Q000187:drug effects*; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism*
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins