K. O'Reilly et al., "mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt," Cancer Res, 66:1500—8, 2006. (Cited in 95 papers)
It's known that rapamycin inhibits lymphoma growth but not solid tumor growth. Rapamycin activates Akt — an enzyme upstream of the protein mTOR, which is crucial to cell survival. In 2006, Sloan-Kettering oncologist Neal Rosen and collaborators illustrated in human tumor cells that inhibiting mTOR does indeed activate Akt. In addition, they short-circuited Akt-mediated cell survival by blocking upstream insulin-like growth factor (IGF)-I, while inhibiting mTOR, and showed improved antitumor action of rapamycin.
Hitting the mTOR pathway in two places in tumor cells decelerates cell growth while speeding up cell death. "You're kind of putting your foot on the accelerator and the brake at the same time," explains David Sabatini of the Whitehead Institute for Biomedical Research.
Sabatini warns that the mTOR pathway is still a black ...
