Molecular pathways: The eIF4F translation initiation complex-newopportunities for cancer treatment

The eIF4F complex regulates the cap-dependent mRNA translation process. It is becoming increasingly evident that aberrant activity of this complex is observed in many cancers, leading to the selective synthesis of proteins involved in tumor growth and metastasis. The selective translation of cellular mRNAs controlled by this complex also contributes to resistance to cancer treatments, and downregulation of the eIF4F complex components can restore sensitivity to various cancer therapies. Here, we review the contribution of the eIF4F complex to tumorigenesis, with a focus on its role in chemoresistance as well as the promising use of new smallmolecule inhibitors of the complex, including flavaglines/rocaglates, hippuristanol, and pateamine A.