Abstract:

t Rapamycin is a macrolide compound which was isolated from samples of Streptomyces hygroscopicus found on Easter Island of Rapa Nui by Surendra Sehgal in 1972. TOR (target of rapamycin) was first identified in Saccharomyces cerevisiae by Michael Hall in 1991, which opened the doors to unravel fundamental mechanisms of cell growth and development. TOR or mTOR (mechanistic TOR) is an important molecular integrator that senses signals arising from growth factors, hormones, amino acids and oxygen status, and then integrates these signals to regulate metabolic pathways involving the synthesis of proteins, lipids, and
nucleotides. TOR/mTOR signaling plays a central role in the control of growth and metabolism. Its dysregulation can contribute to a variety of diseases including cancer, aging and diabetes. Rapalogs (rapamycin and its analogs) had been approved by the US FDA for prevention of transplant rejection, treatment of certain cancers including renal cell carcinoma and neuroendocrine tumors. Here, the discovery process of rapamycin and TOR, the physiological role, mechanism and clinical application of TOR signaling pathway are introduced.