MYC oncogenes as potential anticancer targets

MYC genes (c-MYC, N-MYC, L-MYC) orchestrate a wide spectrum of biologically essential processes associated with cell proliferation and growth, metabolism, survival and death, differentiation, tissue remodeling and regeneration, and immune response. c-MYC was the first gene to be discovered in this family, due to homology with the viral oncogene v-MYC identified as a transforming factor in the genome of the avian myelocytomatosis virus MC29. The impaired regulation and/or function of MYC products is/are proven to be involved in the pathogenesis of more than 70% of human malignancies as well as in various animal tumors. The disturbed MYC has been recognized as a key player in cancer formation and progression and is an attractive target for effective anticancer therapeutic strategies. For decades, MYC genes have been considered undruggable due to various factors such as their physiological importance, nuclear localization, which prevents binding of monoclonal antibodies, intrinsically disordered nature, and lack of enzymatic activity and ligand binding sites suitable for small molecule inhibitors. Several approaches to target MYC genes have been developed in recent years, some of which have shown promising results in preclinical studies. In this review, we summarize information about the unique properties of c-MYC and present data about some anticancer therapeutic strategies using small molecules targeting this oncogene. The prospects for developing compounds targeting c-MYC, particularly G-quadruplexes formed in the c-MYC promoter and c-MYC–Max dimerization, are also discussed.