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Department
Pharmaceutical Chemistry
Course
PHC320H1
Professor
Giaever
Semester
Winter

Description
1WntBcatenin signaling and AXIN1 regulate apoptosis triggered by inhibition of v600Ethe mutant kinas BRAF in human melanomaWntBcatenin signaling pathway linked to melanoma pathogenesis and patient survivalv600E BRAF signaling constitutively activated by BRAFmutation inhibits WntBcatenin signaling in human melanoma cellsBcatenin required for PLX4720induced apoptosis of melanomaActivation of WntBcatenin signaling synergyzed with PLX4720 decreased tumor growth increased apoptosisApoptosis decresed Bcatenin AXIN1AXIN1 mediator not marker of apoptosisv600EWntBcatenin signaling AXIN1 regulate efficacy of inhibitors of BRAFManipulation of WntBcatenin pathway can be combined with BRAF inhibitors to treat melanoma2Clinical efficacy of a RAF inhibitor needs broad target blockade in BRAF mutant melanomaTumors dependent on RAFMEKERK pathway Inhibiting BRAF kinase to benefit melanoma patientsPLX4032 inhibitor of BRAF kinase activityaSelectively inhibits RAFMEKERK pathwaybInhibits ERK phosphorylation but no tumor regressioncIncreased drug inhibited ERK phosphorylation but also a positive clinical response tumor
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