MEK inhibitors are clinically active in BRAF V600E melanomas but only marginally so in
KRAS mutant tumors. Here, we found that MEK inhibitors suppress ERK signaling more …

KRAS and BRAF activating mutations drive tumorigenesis through constitutive activation of
the MAPK pathway. As these tumours represent an area of high unmet medical need …

Mitogen-activated protein kinase (MAPK) pathway dysregulation is implicated in> 30% of all
cancers, rationalizing the development of RAF, MEK and ERK inhibitors. While BRAF and …

Abstract The RAS–RAF–MEK–ERK pathway is the most well-studied of the MAPK cascades
and is critical for cell proliferation, differentiation, and survival. Abnormalities in regulation …

Tumors with mutant RAS are often dependent on extracellular signal–regulated kinase
(ERK) signaling for growth; however, MEK inhibitors have only marginal antitumor activity in …

Summary BRAF V600E drives tumors by dysregulating ERK signaling. In these tumors, we
show that high levels of ERK-dependent negative feedback potently suppress ligand …

BRAF inhibitors (BRAFi) induce antitumor responses in nearly 60% of patients with
advanced V600E/K BRAF melanomas. Somatic activating MEK1 mutations are thought to be …

The RAF/MEK/ERK pathway is central to the control of cell physiology, and its dysregulation
is associated with many cancers. Accordingly, the proteins constituting this pathway …

Although BRAF and MEK inhibitors have proven clinical benefits in melanoma, most patients
develop resistance. We report a de novo MEK2-Q60P mutation and BRAF gain in a …

The most frequent genetic alterations in melanoma are gain-of-function (GOF) mutations in
BRAF, which result in RAF–MEK–ERK signaling pathway addiction. Despite therapeutic …