Drug Detail

Information about Afinitor/Certican

Generic Name
Brand Name (US)
Drug Type
mTOR inhibitor
Approval Status
Approved for a non-GIST cancer
Transplant (EU) and Renal cell carcinoma (USA)
Overall Strategy
Oncogenic Signal Path Based
Block KIT Signal Path
Drug Category
mTOR inhibitor

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, survival, and angiogenesis in cancer. mTOR is a critical component of the PI3K/AKT pathway, a key signaling pathway that is frequently dysregulated in many cancers. RAD001 is an mTOR inhibitor that may improve the effectiveness of Gleevec. Phase I/II trials are underway. It has long been speculated that treatment of GIST (and most cancers in general) will eventually be comprised of a "cocktail mixture" of drugs. This is the first such combination to come to clinical trials for GIST.
mTOR is a downstream target in the AKT pathway. AKT is a survival pathway that is activated by KIT and many other receptors. It is hoped that inhibition of KIT and mTOR at the same time will result in increased effectiveness over Gleevec alone.
Note: Prenen et al., have suggested that, when given with imatinib, RAD001 (everolimus) alters the imatinib blood partition in favour of the erythrocyte. The result may be a reduction of imatinib plasma levels possibly making the imatinib ineffective. If this combination is tried outside of a clinical trial, then the treating physician should be familiar with the fourth link under links below. In addition, plasma testing for imatinib levels might be in order.