Translational Medicine for Overcoming Drug-Resistant Tumors

Researchers have identified mechanisms of resistance in BRAF^V600-mutant tumors to BRAF and MEK inhibitors. These mechanisms involve the MAPK signal transduction pathway, the PI(3)K–AKT–mTOR pathway, or the caspase-dependent apoptotic cascade, all of which regulate the formation of the eIF4F eukaryotic translation initiation complex. A quest for the holy grail in molecular therapeutics seeks a final common pathway that could be leveraged to mitigate resistance.

The eIF4F complex is associated with resistance to anti-BRAF, anti-MEK, and anti-BRAF+anti-MEK drug combinations in BRAF^V600-mutant melanoma and other cancer cell lines. To investigate the role of eIF4F complex formation in resistance, investigators tested response of human melanoma ce…