Hitting the Target in BRAF-Mutant Colorectal Cancer
Mené sur 21 patients atteints d'un cancer colorectal métastatique présentant la mutation V600E du gène BRAF, cet essai multicentrique de phase II évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité du vémurafénib
The development of drugs that target specific oncogenic driver mutations has been integral to personalized cancer medicine. BRAF encodes a serine/threonine kinase that is activated by RAS and phosphorylates mitogen-activated extracellular signal–regulated kinase kinase (MEK), leading to downstream activation of the mitogen-activated protein kinase (MAPK)/extracellular signal–regulated kinase (ERK) pathway, a key mediator of cellular proliferation. Somatic mutations causing constitutive activation of BRAF, most commonly a valine-to-glutamic acid substitution at codon 600 (V600E), were first described in human cancer in 2002. It is now known that BRAF mutations are present in approximately 40% to 50% of melanomas, 40% to 45% of papillary thyroid cancers, 20% to 25% of anaplastic thyroid cancers, and 5% to 15% of colorectal cancers and are at a lower prevalence in numerous other tumor types. Moreover, the V600E mutation is the defining genetic event of hairy cell leukemia...
Journal of Clinical Oncology , éditorial en libre accès, 2015