In malignant cells, treatment with REV-ERB agonists and autophagy regulation showed effectiveness in inducing apoptosis. Moreover, REV-ERB agonists impaired GBM growth in vivo, exerted selective anticancer effects, and ameliorated survival along with no overt toxic effects in mouse models. The agonists of REV-ERBs can affect various oncogenic drivers (such as- PIK3CA, BRAF, and HRAS) and can also continue in TP53 absence and under various hypoxic conditions. The gene discussed is PIK3CA; the disease is glioblastoma.