With the discovery of rapamycin 45 years ago, studies in the mechanistic target of
rapamycin (mTOR) field started 2 decades before the identification of the mTOR kinase.
Over the years, studies revealed that the mTOR signaling is a master regulator of
homeostasis and integrates a variety of environmental signals to regulate cell growth,
proliferation, and metabolism. Deregulation of mTOR signaling, particularly hyperactivation,
frequently occurs in human tumors. Recent advances in molecular profiling have identified
mutations or amplification of certain genes coding proteins involved in the mTOR pathway
(eg, PIK3CA, PTEN, STK11, and RICTOR) as the most common reasons contributing to mTOR
hyperactivation. These genetic alterations of the mTOR pathway are frequently observed
in lung neoplasms and may serve as a target for personalized therapy. mTOR inhibitor
monotherapy has met limited clinical success so far; however, rational drug combinations
are promising to improve efficacy and overcome acquired resistance. A better understanding
of mTOR signaling may have the potential to help translation of mTOR pathway inhibitors
into the clinical setting.
