Chapter 12 - Inhibition of Translation Initiation as a Novel Paradigm for Cancer Therapy

Abstract

Publisher Summary This chapter discusses the role and expression of translation initiation factors in cancer. The regulation of gene expression at the level of translation initiation is critical for proper control of cell growth, proliferation, differentiation, and apoptosis. Deregulation of translation initiation is frequently observed in tumors and plays an important role in the genesis, progression, and maintenance of some cancers. This is because unrestricted translation favors expression of genes that promote cell proliferation, malignant transformation, and cancer progression. Restricting the translation initiation by molecular and chemical genetic approaches reverts the malignant phenotype because it preferentially reduces translation of messenger ribonucleic acids (mRNAs) that code for proteins important for the genesis and progression of cancer. The growing understanding of the structural biology and the mechanistic insight into the translation initiation cascade led to the identification of pharmacological targets for the development of mechanism-specific anticancer agents—a new paradigm for anticancer therapy. Targeting cancer pathways downstream of their cellular signaling networks at the level of translation initiation is more effective and could offer fewer side effects than inhibiting their upstream targets.