Based on what we know now, it is easy to see that in those diseases where Avastin has failed FDA approval, Anti-MEK will do better. MEK is down stream and MEK is involved in much more, including VEGF expression. MEK is part of the MEK/MAPK pathways, it is the door to Mesenchymal transformation (that is it the door to epithelial-mesenchymal transition), and therefore to angiogenesis, and to metastatic spread.
Anti-MEK also removes the negative inhibitory effect of the PTEN driven forces of the PI3K/MTOR pathways.
PTEN inhibits insulin-stimulated MEK/MAPK activation andcell growth by blocking IRS-1 phosphorylation and IRS-1/Grb-2/Sos complex formation in a breast cancer model
- (Liang-Ping Weng1 at al.) The involvement of the Sons of the Sevenless could signify a large implication on the RAS pathway. And Anti-MEK were used as Medication to be used in lung cancer displaying amplification of the K-RAS
Metastatic Colon Cancer is the Primary target!
Only the MTOR inhibitors add to these drugs
Inability of Doxorubicin to add to DTIC in Melanoma is due to amplification of these 2 pathways.
Anti-MEK and MTOR combination will do far better in Melanoma and Pancreatic cancers, mark my words. We just need to brace ourselves to a new set of side effects.