mTORHemmer

mTORHemmer, or mTOR inhibitors, are a class of drugs that inhibit the mechanistic target of rapamycin (mTOR) pathway, a central regulator of cell growth, metabolism and survival. Clinically used agents include sirolimus (rapamycin) and its derivatives everolimus, temsirolimus, and ridaforolimus. They primarily inhibit mTOR complex 1 (mTORC1); prolonged exposure may affect mTORC2 depending on the compound. Inhibiting mTORC1 lowers protein synthesis and cell proliferation and can induce autophagy.

Clinical applications include immunosuppression in organ transplantation and treatment of certain cancers and tuberous sclerosis complex (TSC)–related tumors. Sirolimus is used to prevent organ rejection. Everolimus and temsirolimus are approved for advanced renal cell carcinoma; everolimus is also used for pancreatic neuroendocrine tumors and for TSC-associated renal angiomyolipoma and subependymal giant cell astrocytoma (SEGA). In lymphangioleiomyomatosis (LAM), mTOR inhibitors may slow progression. Research continues into broader oncologic indications and non-oncologic uses.

Adverse effects include mucositis and stomatitis, infections due to immunosuppression, hyperlipidemia, edema, anemia, thrombocytopenia, delayed wound healing, and interstitial pneumonitis. Other issues include metabolic disturbances and dermatologic or ocular effects. Drug interactions are common with CYP3A4 inhibitors or inducers; monitoring trough levels and adjusting dose is often required. Resistance can emerge through feedback activation of AKT and compensatory pathways, limiting long-term efficacy.

Summary: mTOR inhibitors are integral in transplantation and oncology, with expanding research into aging and other disorders. Careful patient selection, monitoring and management of adverse effects and drug interactions are essential.