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Ref Type Journal Article
PMID (24419498)
Authors Grimaldi AM, Simeone E, Ascierto PA
Title The role of MEK inhibitors in the treatment of metastatic melanoma.
Journal Current opinion in oncology
Vol 26
Issue 2
Date 2014 Mar
URL
Abstract Text BRAF and NRAS mutations can exert an oncogenic effect and are a target for novel therapeutic strategies. Selective MEK inhibitors inhibit growth and induce cell death in BRAF and NRAS mutated melanoma cell lines. The first MEK inhibitor (trametinib) has recently been approved for the treatment of BRAF-mutated metastatic melanoma not previously treated with BRAF inhibitors and several more are in clinical development.MEK inhibition is associated with improved response rate, progression-free survival, and overall survival in patients with BRAF-mutated metastatic melanoma. Less clinical benefit has been observed in patients previously treated with a BRAF inhibitor compared with BRAF-inhibitor-naïve patients. Data also suggest clinical activity in patients with NRAS-mutated melanoma. Combination therapy with a BRAF inhibitor may improve the efficacy and reduce BRAF-inhibition-associated side effects.MEK inhibitors represent a new treatment option in BRAF and NRAS mutated melanoma. As monotherapy, MEK inhibitors appear to provide minimal benefit in patients previously treated with a BRAF inhibitor, so they should be reserved for BRAF-inhibitor-naïve patients. Combined BRAF and MEK inhibition seems to provide a greater benefit than BRAF inhibitor monotherapy. MEK inhibition has also shown efficacy in NRAS-mutated patients, for whom there is no specific targeted therapy.

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Molecular Profile Treatment Approach
NRAS G60E MEK2 Inhibitor
NRAS G12Y MEK2 Inhibitor
NRAS G12X MEK inhibitor (Pan)
NRAS G12C MEK inhibitor (Pan)
NRAS G12A MEK2 Inhibitor
NRAS Q61H MEK inhibitor (Pan)
NRAS E63K MEK2 Inhibitor
NRAS G12X MEK2 Inhibitor
NRAS Q61E MEK1 Inhibitor
NRAS G12X MEK1 Inhibitor
NRAS G13S MEK inhibitor (Pan)
NRAS G13S MEK1 Inhibitor
NRAS I24N MEK1 Inhibitor
NRAS G13S MEK2 Inhibitor
NRAS T50I MEK2 Inhibitor
NRAS Q61R MEK2 Inhibitor
NRAS G13R MEK2 Inhibitor
NRAS E63K MEK inhibitor (Pan)
NRAS Q61R MEK1 Inhibitor
NRAS G12C MEK1 Inhibitor
NRAS Q61H MEK1 Inhibitor
NRAS G12N MEK2 Inhibitor
NRAS Q61H MEK2 Inhibitor
NRAS G13X MEK inhibitor (Pan)
NRAS G12C MEK2 Inhibitor
NRAS G12V MEK2 Inhibitor
NRAS T58I MEK2 Inhibitor
NRAS Q61P MEK1 Inhibitor
NRAS G60E MEK inhibitor (Pan)
NRAS T58I MEK1 Inhibitor
NRAS Q61P MEK inhibitor (Pan)
NRAS G12D MEK inhibitor (Pan)
NRAS G13R MEK inhibitor (Pan)
NRAS G12S MEK1 Inhibitor
NRAS G12D MEK1 Inhibitor
NRAS Q61K MEK1 Inhibitor
NRAS A146T MEK1 Inhibitor
NRAS G12A MEK inhibitor (Pan)
NRAS S65C MEK1 Inhibitor
NRAS G13V MEK1 Inhibitor
NRAS G13X MEK2 Inhibitor
NRAS Q61L MEK1 Inhibitor
NRAS G13D MEK1 Inhibitor
NRAS G13D MEK2 Inhibitor
NRAS G12Y MEK inhibitor (Pan)
NRAS G12S MEK2 Inhibitor
NRAS Q61R MEK inhibitor (Pan)
NRAS T50I MEK1 Inhibitor
NRAS G13C MEK2 Inhibitor
NRAS I24N MEK inhibitor (Pan)
NRAS G12N MEK1 Inhibitor
NRAS G13V MEK inhibitor (Pan)
NRAS Q61E MEK inhibitor (Pan)
NRAS G12D MEK2 Inhibitor
NRAS Q61L MEK inhibitor (Pan)
NRAS S65C MEK2 Inhibitor
NRAS Q61X MEK1 Inhibitor
NRAS G13X MEK1 Inhibitor
NRAS G12R MEK2 Inhibitor
NRAS G13C MEK inhibitor (Pan)
NRAS G13A MEK2 Inhibitor
NRAS Q61X MEK2 Inhibitor
NRAS Q61K MEK inhibitor (Pan)
NRAS S65C MEK inhibitor (Pan)
NRAS T58I MEK inhibitor (Pan)
NRAS E63K MEK1 Inhibitor
NRAS G13A MEK inhibitor (Pan)
NRAS A146T MEK2 Inhibitor
NRAS G12S MEK inhibitor (Pan)
NRAS A146T MEK inhibitor (Pan)
NRAS G60E MEK1 Inhibitor
NRAS G12V MEK1 Inhibitor
NRAS G13V MEK2 Inhibitor
NRAS Q61K MEK2 Inhibitor
NRAS Q61E MEK2 Inhibitor
NRAS Q61P MEK2 Inhibitor
NRAS G12R MEK1 Inhibitor
NRAS G12V MEK inhibitor (Pan)
NRAS G13D MEK inhibitor (Pan)
NRAS Q61L MEK2 Inhibitor
NRAS Q61X MEK inhibitor (Pan)
NRAS G13C MEK1 Inhibitor
NRAS G13R MEK1 Inhibitor
NRAS G13A MEK1 Inhibitor
NRAS G12A MEK1 Inhibitor
NRAS G12R MEK inhibitor (Pan)
NRAS T50I MEK inhibitor (Pan)
NRAS G12Y MEK1 Inhibitor
NRAS I24N MEK2 Inhibitor
NRAS G12N MEK inhibitor (Pan)
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References