The Yin and Yang functions of the Myc oncoprotein in cancer development and as targets for therapy

Abstract: The Myc proto-oncoprotein coordinates a number of normal physiological processes necessary for growth and expansion of somatic cells by controlling the expression of numerous target genes. Deregulation of MYC as a consequence of carciogenic events enforces cells to undergo a transition to a hyperproliferative state. This increases the risk of additional oncogenic mutations that in turn can result in further tumor progression. However, Myc activation also provokes intrinsic tumor suppressor mechanisms including apoptosis, cellular senescence and DNA damage responses that act as barriers for tumor development and therefore needs to be overcome during tumorigenesis. Myc thus possesses two seemingly contradictory “faces” here referred to as “Yin and Yang”. Observations that many tumor suppressor pathways remain intact but are latent in tumor cells opens the possibility that pharmacological inhibition of the Yin or activation of the Yang functions can prevail and offer new attractive approaches for treating diverse types of cancer. [Copyright &y& Elsevier]