Welcome back to Rad Onc Smart Review! This is Episode 38: Oncogenic Pathways: RAS/MAPK, PI3K/AKT/mTOR, and HIF-1α. In our previous discussions, we've explored how cells sense and repair DNA damage, and how they make life-or-death decisions through apoptosis. Today, we're shifting our focus to some of the major signaling pathways that, when dysregulated, drive cancer development and can profoundly influence a tumor's response to radiation therapy. We'll dissect the RAS/RAF/MEK/ERK pathway, a critical engine for cell proliferation; the PI3K/AKT/mTOR pathway, a master regulator of cell growth, survival, and metabolism; and the HIF-1α pathway, which allows cells to adapt to hypoxic conditions. We'll also discuss how these pathways are commonly altered in cancer and contribute to radioresistance, and touch upon strategies to target them therapeutically.