Harnessing senescence to control PI3K/AKT/mTORC pathway-driven cancer through the metabolic intervention

Abstract

Oncogene-induced senescence (OIS) is a critical anti-tumour mechanism by arresting cell proliferation following oncogenic activation in normal cells. Cell cycle withdrawal along with senescence-associated secretory phenotype, deregulated metabolism and macromolecular changes are the hallmarks of cellular senescence. The PI3K/AKT/mTORC1 pathway is a key signalling pathway for homeostatic control of cell growth, proliferation, and survival. Molecular aberrations in the PI3K/AKT/mTORC1 signalling pathway have been identified in one third of solid tumours and more than 40 cancer types. Paradoxically, PI3K/AKT/mTORC1 hyperactivation causes a senescence-like phenotype in non-transformed cells. Whi..