Versatile function of AMPK signaling in osteosarcoma: An old player with new emerging carcinogenic functions.

AMP-activated protein kinase (AMPK) signaling has a versatile role in Osteosarcoma (OS), an aggressive bone malignancy with a poor prognosis, particularly in cases that have metastasized or recurred. This review explores the regulatory mechanisms, functional roles, and therapeutic applications of AMPK signaling in OS. It focuses on the molecular activation of AMPK and its interactions with cellular processes like proliferation, apoptosis, and metabolism. The uncertain role of AMPK in cancer is also discussed, highlighting its potential as both a tumor suppressor and a contributor to carcinogenesis. The therapeutic potential of targeting AMPK signaling in OS treatment is examined, including direct and indirect activators like metformin, A-769662, resveratrol, and salicylate. Further research is needed to determine dosing, toxicities, and molecular mechanisms responsible for the anti-osteosarcoma effects of these compounds. This review underscores the complex involvement of AMPK signaling in OS and emphasizes the need for a comprehensive understanding of its molecular mechanisms. By elucidating the role of AMPK in OS, the aim is to pave the way for innovative therapeutic approaches that target this pathway, ultimately improving the prognosis and quality of life for OS patients.