Untangling the Role of MYC in Sarcomas and Its Potential as a Promising Therapeutic Target.

MYC plays a pivotal role in the biology of various sarcoma subtypes, acting as a key regulator of tumor growth, proliferation, and metabolic reprogramming. This oncogene is frequently dysregulated across different sarcomas, where its expression is closely intertwined with the molecular features unique to each subtype. MYC interacts with critical pathways such as cell cycle regulation, apoptosis, and angiogenesis, amplifying tumor aggressiveness and resistance to standard therapies. Furthermore, MYC influences the tumor microenvironment by modulating cell-extracellular matrix interactions and immune evasion mechanisms, further complicating therapeutic management. Despite its well-established centrality in sarcoma pathogenesis, targeting MYC directly remains challenging due to its "undruggable" protein structure. However, emerging therapeutic strategies, including indirect MYC inhibition via epigenetic modulators, transcriptional machinery disruptors, and metabolic pathway inhibitors, offer new hope for sarcoma treatment. This review underscores the importance of understanding the intricate roles of MYC across sarcoma subtypes to guide the development of effective targeted therapies. Given MYC's central role in tumorigenesis and progression, innovative approaches aiming at MYC inhibition could transform the therapeutic landscape for sarcoma patients, providing a much-needed avenue to overcome therapeutic resistance and improve clinical outcomes.