Sunday, January 26, 2014

In Melanoma, Tribulations of the MITF gene!

The gene is a "wild" gene and can auto-regulate, 2 charateristics that make MITF a dangerous gene!   Moreover, it is implicated in cellular differentiation, it regulates the BCL-2, and shows up when resistance to BRAF inhibitor come to be demonstrated.  It causes a deformation and intervene in cellular ability to resist Hypoxia.  Therefore VEGF amplification is a secondary event meaning it is not a driver Mutation, and Anti-VEGF will have a minimal effect in Melanoma.(This is debatable in Uveal melanoma However - Here it is the GNAQ/GNA11 thing! And PKC and MEK inhibitors may be actors).  Mutations in MITF lead to Tietz syndrome[5] and Waardenburg syndrome type IIa.[6]wikipedia
Blocking Wnt 3a, and the Cyclic AMP could be meaningful and alpha MSH could be a bio-marker for BRAF resistance.  Look at PAX3 role and POU3F2!   Interaction with LEF-1 is under scrutiny.   Briefly, we have our eyes on Melanoma and its activity.  The Melanocortin Receptor is also under review...Briefly we know that the cell has predicted that MITF is an agent of differentiation and adaptation (splicing and miRNA 211), it also has planned that if the cell cannot differentiate and adapt, it should quickly die through apoptosis...let melanoma cell choose this natural pass for the cure!
?Does failure to Braf points to susceptibility to Cisplatin or Melphalan?  good question to explore, again is alpha MSH a meaningful Bio-marker under these circumstances?  a good question to further explore!
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