The regulation of protein synthesis in cancer

Translational control of cancer is a multifaceted process, involving alterations in translation factor levels and activities that are unique to the different types of cancers and the different stages of disease. Translational alterations in cancer include adaptations of the tumor itself, of the tumor microenvironment, an integral component in disease, and adaptations that occur as cancer progresses from development to local disease and ultimately to metastatic disease. Adaptations include the overexpression and increased activity of specific translation factors, the physical or functional loss of translation regulatory components, increased production of ribosomes, selective mRNA translation, and alteration of signal transduction pathways to permit unfettered activation of protein synthesis. There is intense clinical interest to capitalize on the emerging new understanding of translational control in cancer by targeting specific components of the translation apparatus that are altered in disease for the development of specific cancer therapeutics. Clinical trial data are nascent but encouraging, suggesting that translational control constitutes an important new area for drug development in human cancer.