Mushrooms, recognized for their culinary and medicinal applications, are emerging as promising autophagy modulators in cancer therapy. Autophagy is cellular degradation triggered by organelle damage, protein aggregation, metabolic disturbances, or nutrient scarcity. It contributes to the suppression of early tumor development and the promotion of cancer cell survival at advanced stages. This review systematically assesses the current evidence on the anticancer potential of mushrooms and their bioactive compounds, focusing on the ability of these mushrooms and their bioactive compounds to modulate autophagy. The review lists over 18 mushroom species (e.g., Ganoderma lucidum, Cordyceps, Phellinus) and 28 bioactive compounds (such as Ganoderic acid DM, Cordycepin, Hispidin) that affect autophagy, demonstrating efficacy against 15 cancer types, including colorectal, lung, breast, and liver cancers. Essential compounds modulate autophagy through phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/Mammalian target of rapamycin (mTOR), AMP-activated protein kinase (AMPK), and Beclin-1 pathways, resulting in notable anticancer effects. G. lucidum extracts significantly reduced colorectal tumor growth by up to 60% in vivo. Additionally, Cordycepin induced autophagic cell death in lung cancer cells, with IC50 values as low as 25 μmol/L. The findings highlight the potential of mushrooms as low-toxicity adjuvants to conventional therapies, providing advantages such as immune modulation and antioxidant activity. Mushrooms and their bioactive components present promising avenues for cancer therapy through the modulation of autophagy. The context-dependent effects of autophagy, along with the limited clinical evidence, present considerable challenges. Future clinical trials must focus on developing standardized extracts and personalized approaches to effectively translate this potential into clinical practice.
