IndraLab
Statements
sparser
"In vitro studies have shown that in the presence of oncogenic RAS proteins, kinase-impaired BRAF forms a complex with CRAF and leads to hyperactivation of the CRAF/MEK/ERK cascade, suggesting MEK inhibitors or CRAF inhibitors may benefit patients with concomitant kinase-impaired BRAF mutation and activating RAS mutation [ xref , xref ]."
sparser
"Selective inhibition of B-Raf drives oncogenic RAS-dependent BRAF binding to C-Raf, CRAF activation and mitogen-activated protein kinase kinase (MEK)-extracellular signal regulated kinase (ERK) signalling, revealing another paradigm of BRAF-mediated signalling that promotes tumour progression [ xref ]."
sparser
"Moreover, BRAF inhibitors drive RAS-dependent BRAF binding to CRAF, CRAF activation, and MEK-ERK signaling in oncogenic RAS [ xref ] revealing a paradigm of BRAF-mediated signaling that promotes tumour progression with clinical implications [ xref ] and highlighting the importance of understanding pathway signaling in clinical practice and of genotyping tumours prior to administering BRAF-selective drugs, to identify patients who are likely to respond and also to identify patients who may experience adverse effects such as increased invasion [ xref ]."
sparser
"N-RAS mutations have been identified in 15%–20% of cutaneous melanoma and are presumed to be one of the important drivers of oncogenesis. xref A somatic mutation in the N-RAS gene causes constitutive activation of the N-RAS protein, which leads to the successive activation of downstream serine/threonine kinases, which promote cell cycle progression, cellular transformation, and enhanced cell survival. xref The overexpression of growth factor receptors, such as epidermal growth factor receptor, c-Met, platelet-derived growth factor receptor (PDGFR), fibroblast growth factor receptor, and c-KIT is also implicated as a mechanism of cellular growth and transformation in RAS-driven melanomas. xref , xref The most important downstream mediators of activated RAS are the serine/threonine kinases B-RAF and C-RAF, which are activated following RAS binding."