Mammalian target of rapamycin inhibition

Abstract

The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that has been increasingly recognized as key to the regulation of cell growth and proliferation. mTOR either directly or indirectly regulates translation initiation, actin organization, tRNA synthesis, ribosome biogenesis, and many other key cell maintenance functions, including protein degradation and transcription functions. Inhibition of mTOR blocks traverse of the cell cycle from the G1 to S phase. Preclinical data show inhibition of tumor growth in a number of cell lines and xenograft models. Clinical trials are ongoing. In metastatic renal cell cancer, both tumor regression and prolonged stabilization have been noted. mTOR inhibition appears to be a key pathway that may be useful in antitumor therapy. Renal cell cancer may be particularly susceptible through both the translation inhibition pathway and pathways that enhance HIF-1alpha gene expression, a factor believed to stimulate growth in metastatic renal cell cancer. Additional clinical trials that use agents that inhibit mTOR are ongoing.