EVEROLIMUS

Blocking mTOR-a central regulator of cancer-cell growth and metabolism

The mammalian target of rapamycin (mTOR) is an intracellular protein that acts as a central regulator of multiple signaling pathways (IGF, EGF, PDGF, VEGF, amino acids) that mediate abnormal growth, proliferation and angiogenesis in cancer.^1,2 mTOR is a critical component of the PI3K/AKT pathway, a key signaling pathway that is frequently dysregulated in many cancers.¹

RAD001 is an oral agent that specifically blocks the mTOR protein kinase activity. By inhibiting cell proliferation, cancer cell metabolism and angiogenesis, RAD001 may provide clinical benefit to patients with cancer.

RAD001 may inhibit angiogenic activity by decreasing HIF1α and tumoral VEGF production, and inhibiting pericyte and endothelial cell proliferation.²

RAD001 is now being investigated in Phase I to III clinical trials in multiple tumor types, including neuroendocrine tumors, renal cell carcinoma, and colorectal, lung and breast cancers.

All compounds are either investigational or studied in new indications. Efficacy and safety have not been established. There is no guarantee that they will become commercially available.

1. Bjornsti M-A, Houghton PJ. The TOR pathway: a target for cancer therapy. Nat Rev Cancer. 2004;4:335-348.
2. O’Reilly TM, Wood JM, Littlewood-Evans A, et al. Differential anti-vascular effects of mTOR or VEGFR pathway inhibition: a rational basis for combining RAD001 and PTK787/ZK222584. Presented at: 96th Annual Meeting of the American Association for Cancer Research. April 16-20, 2005; Anaheim, Calif. Abstract 3038.