A protein named GMI, derived from a relative of Reishi (Ganoderma microsporum), was found to kill drug-resistant lung cancer cells through two distinct pathways. In standard, drug-sensitive lung cancer cells (H1975), GMI triggered apoptosis (programmed cell suicide). Crucially, in cells that had developed osimertinib resistance, GMI induced a self-eating cell death process called autophagy. Confirming this mechanism, blocking autophagy effectively reduced GMI's killing effect. This breakthrough is the first to show GMI's ability to overcome a major clinical challenge—drug resistance—by switching its cell death strategy.