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[Update on clinical activity of CCI779 (temsirolimus), mTOR inhibitor]
Nicolas Mounier1, Stéphane Vignot, Jean-Philippe Spano
1Service d'onco-hématologie, Hôpital de l'Archet 1, 151, route de Saint-Antoine-de-Ginestière, 06202 Nice.
Abstract:
Temsirolimus (CCI779), an intravenous analog of rapamycin, presents immunosuppressive properties and also antiproliferative activity. Its principal target is the mTOR serine/threonin kinase which controls the initiation of the transcription of many ARNm implicated in carcinogenesis. Breast cancers, glioblastoma and renal cell carcinoma were particularly studied with response rates from 10 to 20 %. In haematology, mantle-cell lymphoma is of particular interest because of constitutional activation of cyclin D1 (response rate of 40 %). As a whole these data define temsirolimus as a promising new drug. Current and further developments are based on its association with chemotherapy in a concomitant or sequential way.
Insights
Temsirolimus, an mTOR inhibitor, shows antiproliferative effects against cancers like breast, glioblastoma, and renal cell carcinoma. It is particularly effective in mantle-cell lymphoma, indicating its promise as a new cancer therapeutic.
Area of Science:
- Oncology
- Pharmacology
Background:
- Temsirolimus (CCI779) is an intravenous rapamycin analog.
- It exhibits immunosuppressive and antiproliferative properties.
- Its primary target is the mTOR serine/threonine kinase, crucial in carcinogenesis.
Purpose of the Study:
- To evaluate the efficacy of temsirolimus in various cancers.
- To identify specific cancer types with notable response rates.
- To explore the potential of temsirolimus as a novel therapeutic agent.
Main Methods:
- Clinical studies investigating temsirolimus in breast cancer, glioblastoma, and renal cell carcinoma.
- Evaluation of response rates in these solid tumors.
- Assessment of temsirolimus in hematological malignancies, specifically mantle-cell lymphoma.
Main Results:
- Observed response rates of 10-20% in breast cancer, glioblastoma, and renal cell carcinoma.
- Achieved a 40% response rate in mantle-cell lymphoma, linked to cyclin D1 activation.
- These findings highlight temsirolimus's therapeutic potential.
Conclusions:
- Temsirolimus demonstrates significant promise as a novel anti-cancer drug.
- Its efficacy is particularly noted in mantle-cell lymphoma.
- Future research will focus on combination therapies with chemotherapy.
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