Abstract
Among the transcriptional regulators of cell fate, c-Myc is one of the most frequently deregulated oncogenes, exerting pleiotropic effects on cellular metabolism, survival, and stress adaptation. C-Myc occupies a pivotal position at the intersection of autophagy and senescence, two essential, yet paradoxical processes in cancer biology. Autophagy can both suppress tumor formation and support the survival of established tumors. In contrast, senescence acts as a barrier to malignant transformation but can also promote tumor progression through the senescence-associated secretory phenotype. C-Myc modulates both autophagy and senescence in a highly context-dependent manner. It acts as either an inducer or a suppressor depending on cellular state and microenvironmental conditions. This dual regulatory capacity underscores its role as a central hub in cell fate decisions. In this review, we first summarize how c-Myc, autophagy, and senescence contribute to tumor biology. We then highlight the molecular mechanisms through which c-Myc regulates autophagy and senescence. We examine how these interactions influence cancer progression. Finally, we discuss emerging therapeutic strategies and clinical trials targeting the c-Myc-mediated autophagy/senescence axis. We also address future challenges and opportunities for exploiting this network in precision oncology.
