Global Targeting mTOR in Cancer: Thinking beyond Rapamycin

• 作 者: KerYu;
• 机 构: Principal Research Scientist ⅢWyeth Research USA
• 出 处: (BITs 3rd Annual World Cancer Congress-2010, Breast Cancer C
• 发表日期: 2010年期

　　The mammalian target of rapamycin (mTOR) is a major component of the PI3K/AKT signaling pathway that is dysregulated in 50% of all human malignancies.Rapamycin and its analogs partially inhibit mTOR through allosteric binding to mTOR complex-1 (mTORC 1) but not mTOR complex-2 (mTORC2), an emerging player in cancer.As the first-generation mTOR inhibitors, rapamycin and its analogs (rapalogs) have proven effective in a range of preclinical models.In the clinic, rapalogs have demonstrated important clinical benefits, particularly against endometrial cancer,mantle cell lymphoma and renal cancer.Nevertheless, the overall objective response rates in major solid tumors achieved with single-agent rapalog therapy have been modest.The limited effectiveness of rapamycin as cancer therapy can be explained by its biochemical mechanism as well as its complex and variable signaling responses in cancer cells.