[Farnesyl transferase inhibitors (anti-Ras). A new class of anticancer agents].
Ras genes are frequently activated in human tumours. The role of their product, the P21 proteins, in the transduction of the mitogenic signal makes them attractive targets for an anti-neoplastic therapy. The p21 ras proteins are linked to the plasma membrane and transformed into an active form for signal transmission. Their effect is to mediate the effects of growth factors. Two drug families, the Benzodiazepine peptidomimetics and the CAAX tetrapeptides which inhibit the farnesylation of P21-Ras proteins abolish the transforming properties of mutated P21. These promising drugs could rapidly have clinical applications. They have been shown to be highly active at precise concentrations on ras-transformed cells but at the same concentrations are not toxic for untransformed cells. They do not effect other similar enzyme systems within the cell, underlining their selective capacity. Theoretically anti-ras therapy could only suspend cell transformation although it might be possible that if given long enough, a lethal threshold could be reached.
Levy
R
R
Unité d'Onco-Hématologie, Hôpital Laennec, Paris.
D019883:Alkyl and Aryl Transferases; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001569:Benzodiazepines / Q000627:therapeutic use; D051231:Farnesyltranstransferase; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D017368:Protein Prenylation; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics / Q000378:metabolism; D014166:Transferases / Q000037:antagonists & inhibitors* / Q000627:therapeutic use
D000970:Antineoplastic Agents; D001569:Benzodiazepines; D014166:Transferases; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)
Les inhibiteurs de la farnésyl-transférase (anti-Ras). Une nouvelle classe d'anti-cancéreux.