Melanoma adapts to RAF/MEK inhibitors through FOXD3-mediated upregulation of ERBB3

The mechanisms underlying adaptive resistance of melanoma to targeted therapies remain unclear. By combining ChIP sequencing with microarray-based gene profiling, we determined that ERBB3 is upregulated by FOXD3, a transcription factor that promotes resistance to RAF inhibitors in melanoma…”

First Treatment That Targets Melanomas with NRAS Mutations

A phase II study suggests that a MEK inhibitor drug benefits people who have melanomas with NRAS mutations, which currently have no targeted treatments. The drug, called MEK162, shrank tumors in 20% of NRAS-mutated melanoma patients (6 out of 30). MEK162 also shrank tumors in 20% of BRAF-mutated melanoma patients (8 out of 41), as well as tumors that had spread to the brain in two patients. This study is registered with ClinicalTrials.gove as number NCT01320085, and is now recruiting more patients with NRAS mutations.

MEK Inhibitor Active in NRAS-Mutated Melanoma

The MEK inhibitor MEK162 is the first agent to show some activity in patients with NRAS– and BRAF-mutated advanced melanoma, according to the conclusions of a phase II study, evaluating the drug’s safety and efficacy, published in Lancet Oncology. In addition, treatment with MEK162 resulted in the shrinkage of target brain metastases in two patients.

Research paper here:

New Phase III study will test BRAF/MEK combination therapy in melanoma patients with BRAF positive mutation after following surgery

The London-based company, GSK has stared a phase III trial called “COMBI-AD” that will test the combination of a BRAF and MEK inhibitor, dabrafenib and trametinib in patients with BRAF V600E mutation-positive melanoma who have had surgery to remove their tumors (adjuvant setting). The placebo-controlled trial is testing how long the combo treatment can delay or prevent cancer recurrence in these high-risk patients. Two phase III combination trials are currently ongoing to test the combination versus monotherapy in metastatic BRAF-positive melanoma patients. 

Europe Accelerates Trametinib Review

The European Medicines Agency has granted a speedy review of trametinib, an experimental MEK inhibitor made by pharmaceutical company GlaxoSmithKline. The firm’s application for a European license includes findings from two studies of melanomas that have BRAF V600 mutations: a phase III trial comparing trametinib to two standard chemotherapy drugs (dacarbazine and paclitaxel) and a phase I/II trial comparing trametinib alone and in combination with the experimental BRAF-inhibitor dabrafenib. If approved, trametinib could be available to people with melanoma within 6 months.

Plexxikon updates Zelboraf Phase 1 data on BRAF V600E mutation-positive melanoma

Plexxikon today announced that updated Phase 1 clinical data of Zelboraf (vemurafenib) were presented at the Society for Melanoma Research (SMR) 2012 Congress, held November 8-11 in Los Angeles, CA.

Combined BRAF and MEK Inhibition Improves Outcome in Metastatic Melanoma

The combination of dabrafenib and trametinib is safe and effective in BRAF-mutant melanoma.

Watchdog approves skin cancer drugs ipilimumab and vemurafenib

Patients with an advanced form of skin cancer were given new hope today after the health watchdog recommended that two life-extending treatments should be available on the NHS.

PLOS ONE: The Prognostic Value of BRAF Mutation in Colorectal Cancer and Melanoma: A Systematic Review and Meta-Analysis

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