Acquired resistance to BRAF inhibitors often involves MAPK re-activation, yet the MEK
inhibitor trametinib showed minimal clinical activity in melanoma patients that had …

One-third of BRAF-mutant metastatic melanoma patients treated with combined BRAF and
MEK inhibition progress within 6 months. Treatment options for these patients remain …

Background In melanoma, dysregulation of the MAPK pathway, usually via BRAF V600 or
NRAS Q61 somatic mutations, leads to constitutive ERK signaling. While BRAF inhibitors …

The discovery of the role of the RAS/RAF/MEK/ERK pathway in melanomagenesis and its
progression have opened a new era in the treatment of this tumor. Vemurafenib was the first …

Vemurafenib and dabrafenib, two potent tyrosine kinase inhibitors (TKIs) of the BRAF V600E
kinase, are highly effective in the treatment of a BRAF V600-mutant metastatic melanoma …

Background: MEK1 mutations in melanoma can confer resistance to BRAF inhibitors,
although preexisting MEK1P124 mutations do not preclude clinical responses. We sought to …

The efficacy of selective BRAF inhibitors has now been established in the 50% of patients
with metastatic melanoma whose tumors harbor activating mutations. However, for the vast …

The introduction of tyrosine kinase inhibitors for the treatment of malignant melanoma has
led to unprecedented response rates with superior overall survival rates in patients with …

9005 Background: Dual inhibition of the MAP kinase (MAPK) pathway with dabrafenib (D)
and trametinib (T) in combination has demonstrated clinical benefit compared to D alone in …

Most melanomas are driven by activation of the extracellular regulated kinase (ERK)
pathway. In approximately 40% of cutaneous melanomas, this activation is due to a BRAF …