Journal
BRITISH JOURNAL OF HAEMATOLOGY
Volume 145, Issue 5, Pages 569-580Publisher
WILEY
DOI: 10.1111/j.1365-2141.2009.07657.x
Keywords
mammalian target of rapamycin; leukaemia; signal transduction; lymphoma; sirolimus
Categories
Funding
- Larry and Helen Hoag Foundation Clinical Translational Research Career Development
- ASCO Young Investigator and Career Development
- Leukaemia and Lymphoma Society (DTT)
- NIH [1K08 CA104882-01A1, IRG-78-002-30, CA102646, CA1116660]
- American Cancer Society,
- Children's Cancer Fund
- Florence R.C. Murray Program at the Children's Hospital of Philadelphia
- WW Smith Charitable Trust (VIB)
- ACS [RSG0507101]
- Weinberg Fund of the Children's Hospital of Philadelphia (SAG)
- NATIONAL CANCER INSTITUTE [R01CA102646, K08CA104882] Funding Source: NIH RePORTER
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The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that functions as a key regulator of cell growth, protein synthesis, and cell-cycle progression through interactions with a number of signalling pathways, including PI3K/AKT, ras, TCL1, and BCR/ABL. Many haematological malignancies have aberrant activation of the mTOR and related signalling pathways. Accordingly, mTOR inhibitors, a class of signal transduction inhibitors that were originally developed as immunosuppressive agents, are being investigated in preclinical models and clinical trials for a number of haematological malignancies. Sirolimus and second-generation mTOR inhibitors, such as temsirolimus and everolimus, are safe and relatively well-tolerated, making them potentially attractive as single agents or in combination with conventional cytotoxics and other targeted therapies. Promising early clinical data suggests activity of mTOR inhibitors in a number of haematological diseases, including acute lymphoblastic leukaemia, chronic myeloid leukaemia, mantle cell lymphoma, anaplastic large cell lymphoma, and lymphoproliferative disorders. This review describes the rationale for using mTOR inhibitors in a variety of haematological diseases with a focus on their use in leukaemia.
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