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Lung Cancer

The Potential Role of mTOR Inhibitors in Non-Small Cell Lung Cancer

Division of Medical Oncology, "S.G. Moscati" Hospital, Avellino, Italy

Key Words. Mammalian target of rapamycin • Sirolimus • Temsirolimus • Everolimus • AP23573 • NSCLC

Correspondence: Cesare Gridelli, M.D., Division of Medical Oncology, "S.G. Moscati" Hospital, Contrada Amoretta, 83100 Avellino, Italy. Telephone: 39-0825-203573; Fax: 39-0825-203556; e-mail: cgridelli{at}libero.it

Disclosure: No potential conflicts of interest were reported by the authors, planners, reviewers, or staff managers of this article.

The mammalian target of rapamycin (mTOR), a serine/threonine kinase, is a downstream mediator in the phosphatidylinositol 3-kinase/Akt signaling pathway, which plays a critical role in regulating basic cellular functions including cellular growth and proliferation. Currently, the mTOR inhibitor rapamycin and its analogues (CCI-779, RAD001, AP23573), which induce cell-cycle arrest in the G₁ phase, are being evaluated in cancer clinical trials. The mTOR inhibitors appear to be well tolerated, with skin reactions, stomatitis, myelosuppression, and metabolic abnormalities the most common toxicities seen. These adverse events are transient and reversible with interruption of dosing. Several pieces of evidence suggest a certain antitumor activity, including tumor regressions and prolonged stable disease, which has been reported among patients with a variety of malignancies, including non-small cell lung cancer (NSCLC). These promising preliminary clinical data have stimulated further research in this setting. Here, we review the basic structure of the pathway together with current results and future developments of mTOR inhibitors in the treatment of NSCLC patients.

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