Trends Biochem Sci. 2026 Mar 25. pii: S0968-0004(26)00032-0. [Epub ahead of print]
Rapamycin, a 'wonder drug', was first reported 50 years ago in two papers in the Journal of Antibiotics, which described an antifungal compound purified from a bacterium isolated from soil samples collected on Easter Island (Rapa Nui). What began as the characterization of a natural product led to the identification of an entirely new signaling cascade, the target of rapamycin (TOR) pathway, and the emergence of a new field in biomedical research. Here, we review the historical and molecular foundations of the TOR field, from the discovery of rapamycin to current models of nutrient sensing, pathway regulation, clinical applications, and future perspectives.
Keywords: mTOR pathway; rapamycin