Sirolimus is FDA-approved for organ transplant recipients and can therefore be prescribed off-label for other purposes at the discretion of a physician.
NCI drug dictionary definition: A drug used to keep the body from rejecting organ and bone marrow transplants. Sirolimus blocks certain white blood cells that can reject foreign tissues and organs. It also blocks a protein that is involved in cell division. It is a type of antibiotic, a type of immunosuppressant, and a type of serine/threonine kinase inhibitor. Sirolimus was previously called rapamycin. Also called Rapamune.
mTOR inhibition: In addition to the immunosuppessive action descibed in the defination above, sirolimus also inhibits mTOR. Here is a quote from the prescribing information: “…sirolimus binds to the immunophilin, FK Binding Protein-12 (FKBP-12), to generate an immunosuppressive complex. The sirolimus:FKBP-12 complex has no effect on calcineurin activity. This complex binds to and inhibits the activation of the mammalian Target Of Rapamycin (mTOR), a key regulatory kinase. This inhibition suppresses cytokine-driven T-cell proliferation, inhibiting the progression from the G1 to the S phase of the cell cycle.”
Manufactured by Wyeth and marketed by Pfizer
Information at Pfizer website: link here
Relevance to GIST: Anecdotally, some GIST patients who have developed resistance to imatinib have been prescribed a combination of sunitinib plus sirolimus by GIST expert physicians.
Clinical Trials with sirolimus