mTOR Caveats

In many tumor types, rapamycin is thought to inhibit mammalian target of rapamycin's regulation of a key transcription factor-hypoxia-inducible factor-1a-that is involved in tumor cell growth and proliferation. A widely used biomarker therefore relies on suppression of this factor as a proxy for mammalian target of rapamycin inhibition. However, a recent report in Current Biology questions whether that particular biomarker is appropriate in all tumor types.

Mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase that regulates cell growth, proliferation and survival as well as protein synthesis and transcription. Hypoxia-inducible factor-1a (HIF-1a), an oxygen-sensitive transcription factor, sits downstream of and is regulated by mTOR. HIF-1a is highly expressed in many tumor types and is known to regulate the expression of genes involved in tumor angiogenesis, metabolism and invasion...