One-third of all sporadic human cancers display aberrant activation of the PI3K/AKT/mTORC1 signalling network, which is essential for homeostatic processes involving cell growth, proliferation, and survival. Fine-tuned regulation of this rheostat is, therefore, an intrinsic safeguard against malignant progression. Despite substantial investigation into anti-proliferative therapies targeting the PI3K/AKT/mTORC1 pathway in cancer, a gap remains in our understanding of how persistent signalling promotes arrest in normal cells by oncogene-induced senescence (OIS) and whether this could be exploited to reverse the transformed phenotype. Here, we use transcriptome profiling and whole genome RNAi screening to uncover regulators of PI3K/AKT/mTORC1-dependent OIS. In particular, we identify that suppression of RAS/ERK signalling is required for OIS maintenance while its reactivation potentiates evasion and transformation. Toggling RAS/ERK activity in ovarian cancer cells displaying chronic PI3K/AKT/mTORC1 activation enables switching between cycling and a cytostatic state exhibiting multiple markers of cellular senescence. Together, our findings raise the possibility of combining inhibitors of RAS/ERK signalling with therapies such as checkpoint inhibitors or those that selectively kill senescent cells (senolytics) to combat PI3K/AKT/mTORC1-driven cancers.