A mTOR inhibitor.

Torisel is trade name.

Specific inhibitor of rapamycin kinase.

Inhibits mTOR (rapamycin kinase), which is a intracellular signaling pathway involved in the growth and proliferation of cells and in cell response to hypoxia.

Binds to FKBP-12, an intracellular protein, forming a complex resulting in inhibition of mTOR signaling.

Causes disruption of mTOR signaling impairs production of cell cycle regulating proteins and angiogenesis.

Inhibits angiogenesis, a prominent process in renal cancer.

In patients with advanced renal cell cancer has antitumor activity, acceptable toxicity and improved survival rates.

In poor risk patients in a phase 3 trial temsirolimus had a significantly longer overall survival in renal cancer compared with interferon (10.9 months vs. 7.3 months)(Hudes).

Improves progression free survival in patients with relapsed or refractory mantle cell lymphoma.

An intravenous agent for the treatment of renal cell carcinoma (RCC).

A specific inhibitor of mTOR and interferes with the synthesis of proteins that regulate proliferation, growth, and survival of tumor cells.

Leads to cell cycle arrest in the G1 phase, and also inhibits tumor angiogenesis by reducing synthesis of VEGF.

mTOR refers to the mammalian target of rapamycin.

A kinase enzyme inside the cell that collects and interprets growth and survival signals received by cells.

Kinase activation of mTOR results in activation of downstream effectors with the synthesis of cell cycle proteins such as cyclin D and hypoxia-inducible factor-1a (HIF-1a).

mTOR kinase activation determines whether a malignant tumor cell produces key proteins needed for proliferation, growth, survival, and angiogenesis.

mTOR is activated in tumor cells by growth factor surface receptor tyrosine kinases, oncogenes, and loss of tumor suppressor genes and are important for malignant transformation and progression.

mTOR is important in the biology of renal cancer (RCC) owing to its function in regulating HIF-1a levels.

Mutation or loss of the von Hippel Lindau tumor-suppressor gene is common in renal cell cancer and results in reduced degradation of HIF-1a.

In renal cell tumors, activated mTOR causes accumulation of HIF-1a by increasing synthesis of this transcription factor.

In an international Three-arm phase III study with 626 previously untreated, poor-prognosis patients, temsirolimus, interferon-α and the combination of both agents was compared: Median overall survival improved significantly in the temsirolimus group (10.9 months) compared with interferon-α group (7.3 months) and the combination group (8.4 months).

Adverse reactions include: fatigue, skin rash, stomatitis, hematologic abnormalities, lymphocytopenia, increased triglycerides, hyperglycemia, and hypophosphatemia.

Adverse effect profile of temsirolimus is primarily metabolic in nature.

Associated with lung toxicity, which is increased among patients with abnormal pulmonary functions or history of lung disease.

The recommended dose is 25 mg IV infused over 30–60 minutes once per week until disease progression or until intolerable side effects.

Antihistamine pretreatment is recommended to minimize the risk of an allergic reactions.

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