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Ref Type Journal Article
PMID (28203297)
Authors de Langen AJ, Smit EF
Title Therapeutic approach to treating patients with BRAF-mutant lung cancer: latest evidence and clinical implications.
URL
Abstract Text Lung adenocarcinoma is known for its high rate of somatic mutations and genomic rearrangements. The identification of epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements that sensitize tumors to specific drugs has changed the therapeutic approach and prognosis in these molecularly-defined subgroups. Several other key genetic alterations have been identified, of which BRAF mutations are found in 4% of non-small cell lung cancer (NSCLC) cases. Targeted drugs against BRAF and downstream MEK were recently approved for the treatment of BRAF-positive melanoma and have entered clinical evaluation in NSCLC. In this review we discuss the latest evidence on the treatment of BRAF-mutated NSCLC, including tumor biology, targeted treatment with BRAF and MEK inhibitors, therapeutic resistance and strategies to overcome resistance.

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Molecular Profile Treatment Approach
BRAF L597V MEK1 Inhibitor
BRAF K601N MEK inhibitor (Pan)
BRAF D594Y MEK1 Inhibitor
BRAF T599_V600insEAT MEK inhibitor (Pan)
BRAF S467A MEK inhibitor (Pan)
BRAF T488_Q493delinsK MEK2 Inhibitor
BRAF L485_P490delinsF MEK inhibitor (Pan)
BRAF E586K MEK1 Inhibitor
BRAF T599_V600insETT MEK1 Inhibitor
BRAF G596D MEK inhibitor (Pan)
BRAF D594H MEK inhibitor (Pan)
BRAF V600dup MEK1 Inhibitor
BRAF L597V MEK2 Inhibitor
BRAF G596V MEK inhibitor (Pan)
BRAF F595L MEK2 Inhibitor
BRAF G466R MEK1 Inhibitor
BRAF V487_P492delinsA MEK1 Inhibitor
BRAF A598V MEK1 Inhibitor
BRAF G596C MEK2 Inhibitor
BRAF V600E/K BRAF Inhibitor
BRAF L505H MEK inhibitor (Pan)
BRAF T599_V600insTT MEK1 Inhibitor
BRAF act mut MEK2 Inhibitor
BRAF K601Q MEK1 Inhibitor
BRAF I463S MEK inhibitor (Pan)
BRAF L597R MEK inhibitor (Pan)
BRAF V471F MEK2 Inhibitor
BRAF G464R MEK2 Inhibitor
BRAF V487_P492delinsA MEK inhibitor (Pan)
BRAF T599R MEK inhibitor (Pan)
BRAF G596D MEK1 Inhibitor
BRAF G466R MEK inhibitor (Pan)
BRAF A728V MEK1 Inhibitor
BRAF G464E MEK2 Inhibitor
BRAF D594E MEK inhibitor (Pan)
BRAF A598_T599insARC MEK1 Inhibitor
BRAF V600L MEK inhibitor (Pan)
BRAF G469R MEK2 Inhibitor
BRAF N486_L495del MEK1 Inhibitor
BRAF D594_T599dup MEK inhibitor (Pan)
BRAF D594N MEK inhibitor (Pan)
BRAF G596R MEK inhibitor (Pan)
BRAF V487_P492delinsA MEK2 Inhibitor
BRAF V504_R506dup MEK1 Inhibitor
BRAF L597Q MEK inhibitor (Pan)
BRAF S467A MEK1 Inhibitor
BRAF G469S MEK2 Inhibitor
BRAF V504_R506dup MEK2 Inhibitor
BRAF G464R MEK inhibitor (Pan)
BRAF G469V MEK inhibitor (Pan)
BRAF N486_P490del MEK1 Inhibitor
BRAF G464V MEK inhibitor (Pan)
BRAF L597Q MEK2 Inhibitor
BRAF F468C MEK inhibitor (Pan)
BRAF A598_T599insARC MEK inhibitor (Pan)
BRAF L597R MEK1 Inhibitor
BRAF Q257R MEK1 Inhibitor
BRAF act mut MEK inhibitor (Pan)
BRAF V600_K601delinsE MEK inhibitor (Pan)
BRAF D594Y MEK inhibitor (Pan)
BRAF V600G MEK inhibitor (Pan)
BRAF K601I MEK2 Inhibitor
BRAF L597S MEK1 Inhibitor
BRAF T488_P492del MEK1 Inhibitor
BRAF K601E MEK2 Inhibitor
BRAF L505H MEK2 Inhibitor
BRAF G596C MEK inhibitor (Pan)
BRAF G466V MEK inhibitor (Pan)
BRAF D594E MEK2 Inhibitor
BRAF V600K MEK inhibitor (Pan)
BRAF L485_P490del MEK2 Inhibitor
BRAF V600L RAF Inhibitor (Pan)
BRAF L597Q MEK1 Inhibitor
BRAF G469L MEK inhibitor (Pan)
BRAF G466V MEK1 Inhibitor
BRAF E586K MEK2 Inhibitor
BRAF T599R MEK2 Inhibitor
BRAF A728V MEK inhibitor (Pan)
BRAF L485_P490delinsF MEK1 Inhibitor
BRAF A598V MEK inhibitor (Pan)
BRAF D594A MEK2 Inhibitor
BRAF Q257R MEK inhibitor (Pan)
BRAF N486_L495del MEK inhibitor (Pan)
BRAF act mut MEK1 Inhibitor
BRAF K601Q MEK2 Inhibitor
BRAF L485_P490del MEK1 Inhibitor
BRAF G469L MEK1 Inhibitor
BRAF T599I MEK inhibitor (Pan)
BRAF L485_P490delinsY MEK2 Inhibitor
BRAF A598_T599insV MEK1 Inhibitor
BRAF K601E MEK inhibitor (Pan)
BRAF N486_T491delinsK MEK inhibitor (Pan)
BRAF L597S MEK inhibitor (Pan)
BRAF E586K MEK inhibitor (Pan)
BRAF N486_L495del MEK2 Inhibitor
BRAF T599_V600insETT MEK inhibitor (Pan)
BRAF N486_P490del MEK inhibitor (Pan)
BRAF K601Q MEK inhibitor (Pan)
BRAF K601N MEK1 Inhibitor
BRAF T599R MEK1 Inhibitor
BRAF V600D RAF Inhibitor (Pan)
BRAF V600delinsYM MEK1 Inhibitor
BRAF G596R MEK1 Inhibitor
BRAF F247L MEK inhibitor (Pan)
BRAF M484_N486del MEK1 Inhibitor
BRAF K499E MEK1 Inhibitor
BRAF A598_T599insV MEK inhibitor (Pan)
BRAF T488_P492del MEK2 Inhibitor
BRAF L485_P490delinsY MEK1 Inhibitor
BRAF G469A MEK inhibitor (Pan)
BRAF T599dup MEK1 Inhibitor
BRAF V471F MEK1 Inhibitor
BRAF G466R MEK2 Inhibitor
BRAF V504_R506dup MEK inhibitor (Pan)
BRAF F247L MEK2 Inhibitor
BRAF D594H MEK1 Inhibitor
BRAF V600K BRAF Inhibitor
BRAF G469R MEK1 Inhibitor
BRAF D594A MEK inhibitor (Pan)
BRAF K601I MEK1 Inhibitor
BRAF T599_V600insEAT MEK2 Inhibitor
BRAF I463S MEK2 Inhibitor
BRAF D594H MEK2 Inhibitor
BRAF V471F MEK inhibitor (Pan)
BRAF K601I MEK inhibitor (Pan)
BRAF P490_Q494del MEK inhibitor (Pan)
BRAF L505H MEK1 Inhibitor
BRAF D594Y MEK2 Inhibitor
BRAF D594N MEK2 Inhibitor
BRAF D594_T599dup MEK1 Inhibitor
BRAF V600E BRAF Inhibitor
BRAF V600_K601delinsE MEK2 Inhibitor
BRAF G469V MEK1 Inhibitor
BRAF P490_Q494del MEK2 Inhibitor
BRAF M484_N486del MEK2 Inhibitor
BRAF G469S MEK1 Inhibitor
BRAF G469L MEK2 Inhibitor
BRAF F468C MEK2 Inhibitor
BRAF G469S MEK inhibitor (Pan)
BRAF L597V MEK inhibitor (Pan)
BRAF L485F MEK2 Inhibitor
BRAF G464E MEK inhibitor (Pan)
BRAF G469V MEK2 Inhibitor
BRAF D594A MEK1 Inhibitor
BRAF I463S MEK1 Inhibitor
BRAF G469A MEK1 Inhibitor
BRAF V600delinsYM MEK2 Inhibitor
BRAF N486_T491delinsK MEK1 Inhibitor
BRAF K601T MEK2 Inhibitor
BRAF K601N MEK2 Inhibitor
BRAF F247L MEK1 Inhibitor
BRAF T599dup MEK2 Inhibitor
BRAF A598V MEK2 Inhibitor
BRAF F595L MEK inhibitor (Pan)
BRAF D287H MEK1 Inhibitor
BRAF G464E MEK1 Inhibitor
BRAF T599I MEK1 Inhibitor
BRAF L597P MEK1 Inhibitor
BRAF A728V MEK2 Inhibitor
BRAF L485F MEK1 Inhibitor
BRAF K601T MEK inhibitor (Pan)
BRAF V600_K601delinsE MEK1 Inhibitor
BRAF L597P MEK2 Inhibitor
BRAF L485_P490delinsF MEK2 Inhibitor
BRAF L485_P490delinsY MEK inhibitor (Pan)
BRAF T599dup MEK inhibitor (Pan)
BRAF K601E MEK1 Inhibitor
BRAF T599_V600insTT MEK2 Inhibitor
BRAF P490_Q494del MEK1 Inhibitor
BRAF G469R MEK inhibitor (Pan)
BRAF D287H MEK inhibitor (Pan)
BRAF G464R MEK1 Inhibitor
BRAF V600dup MEK inhibitor (Pan)
BRAF V600L BRAF Inhibitor
BRAF V600D MEK inhibitor (Pan)
BRAF D594E MEK1 Inhibitor
BRAF V600E RAF Inhibitor (Pan)
BRAF G596C MEK1 Inhibitor
BRAF T599I MEK2 Inhibitor
BRAF S467A MEK2 Inhibitor
BRAF G464V MEK2 Inhibitor
BRAF D287H MEK2 Inhibitor
BRAF G466V MEK2 Inhibitor
BRAF T488_P492del MEK inhibitor (Pan)
BRAF A598_T599insARC MEK2 Inhibitor
BRAF K499E MEK inhibitor (Pan)
BRAF V600E/K RAF Inhibitor (Pan)
BRAF A598_T599insV MEK2 Inhibitor
BRAF F468C MEK1 Inhibitor
BRAF T599_V600insEAT MEK1 Inhibitor
BRAF L597S MEK2 Inhibitor
BRAF L485_P490del MEK inhibitor (Pan)
BRAF L597R MEK2 Inhibitor
BRAF N486_T491delinsK MEK2 Inhibitor
BRAF F595L MEK1 Inhibitor
BRAF L597P MEK inhibitor (Pan)
BRAF G464V MEK1 Inhibitor
BRAF M484_N486del MEK inhibitor (Pan)
BRAF V600D BRAF Inhibitor
BRAF G596R MEK2 Inhibitor
BRAF K499E MEK2 Inhibitor
BRAF G596V MEK1 Inhibitor
BRAF V600G RAF Inhibitor (Pan)
BRAF T488_Q493delinsK MEK1 Inhibitor
BRAF V600K RAF Inhibitor (Pan)
BRAF V600G BRAF Inhibitor
BRAF G596V MEK2 Inhibitor
BRAF T599_V600insTT MEK inhibitor (Pan)
BRAF V600dup MEK2 Inhibitor
BRAF T599_V600insETT MEK2 Inhibitor
BRAF V600E MEK inhibitor (Pan)
BRAF L485F MEK inhibitor (Pan)
BRAF D594N MEK1 Inhibitor
BRAF G469A MEK2 Inhibitor
BRAF T488_Q493delinsK MEK inhibitor (Pan)
BRAF N486_P490del MEK2 Inhibitor
BRAF D594_T599dup MEK2 Inhibitor
BRAF V600E/K MEK inhibitor (Pan)
BRAF V600delinsYM MEK inhibitor (Pan)
BRAF Q257R MEK2 Inhibitor
BRAF K601T MEK1 Inhibitor
BRAF G596D MEK2 Inhibitor
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