Eukaryotic initiation factor 4F—sidestepping resistance mechanisms arising from expression heterogeneity

There is enormous diversity in the genetic makeup and gene expression profiles between and within tumors. This heterogeneity leads to phenotypic variation and is a major mechanism of resistance to molecular targeted therapies. Here we describe a conceptual framework for targeting eukaryotic initiation factor (eIF) 4F in cancer—an essential complex that drives and promotes multiple Cancer Hallmarks. The unique nature of eIF4F and its druggability bypasses several of the heterogeneity issues that plague molecular targeted drugs developed for cancer therapy.