Exploiting the mammalian _target of rapamycin pathway in hematologic malignancies
- PMID: 18300753
- DOI: 10.1097/MOH.0b013e3282f3deaa
Exploiting the mammalian _target of rapamycin pathway in hematologic malignancies
Abstract
Purpose of review: This review critically assesses recent research advances in elucidating the role of the mammalian _target of rapamycin pathway in the pathogenesis of hematologic malignancies and the potential of _targeting this signaling pathway to treat such malignancies.
Recent findings: Mammalian _target of rapamycin is a highly conserved serine/threonine protein kinase that controls initiation of mRNA translation, cell cycle progression, and cellular proliferation. Recent dramatic advances in research into cellular signaling by mammalian _target of rapamycin and its effectors, and better understanding of aberrant activation of mammalian _target of rapamycin pathways in hematologic malignancies have stimulated considerable interest in the clinical development of inhibitors that _target this pathway. Numerous clinical trials using mammalian _target of rapamycin inhibitors are ongoing in various hematologic malignancies. Such trials are direct extensions of preclinical work establishing that inhibition of this pathway blocks cell proliferation and/or induces apoptotic cell death, both in vitro and in vivo.
Summary: The role of the mammalian _target of rapamycin pathway in hematologic malignancies is of considerable interest with major clinical/translational relevance. Here, our understanding of the functional roles of the mammalian _target of rapamycin pathway and its deregulation in hematologic malignancies are summarized and resulting clinical/translational efforts discussed.
Similar articles
-
mTOR inhibitors in hematologic malignancies.Clin Adv Hematol Oncol. 2003 Jul;1(7):419-23. Clin Adv Hematol Oncol. 2003. PMID: 16258427 Review.
-
The mammalian _target of the rapamycin (mTOR) kinase pathway: its role in tumourigenesis and _targeted antitumour therapy.Cell Mol Biol Lett. 2005;10(3):479-98. Cell Mol Biol Lett. 2005. PMID: 16217558 Review.
-
Mammalian _target of rapamycin and caspase inhibitors in polycystic kidney disease.Clin J Am Soc Nephrol. 2008 Jul;3(4):1219-26. doi: 10.2215/CJN.05611207. Clin J Am Soc Nephrol. 2008. PMID: 18587045 Review.
-
Mammalian _target of rapamycin (mTOR) pathway signalling in lymphomas.Expert Rev Mol Med. 2008 Feb 4;10:e4. doi: 10.1017/S1462399408000586. Expert Rev Mol Med. 2008. PMID: 18241520 Review.
-
A phase 2 clinical trial of deforolimus (AP23573, MK-8669), a novel mammalian _target of rapamycin inhibitor, in patients with relapsed or refractory hematologic malignancies.Clin Cancer Res. 2008 May 1;14(9):2756-62. doi: 10.1158/1078-0432.CCR-07-1372. Clin Cancer Res. 2008. PMID: 18451242 Clinical Trial.
Cited by
-
Novel CD20 monoclonal antibodies for lymphoma therapy.J Hematol Oncol. 2012 Oct 11;5:64. doi: 10.1186/1756-8722-5-64. J Hematol Oncol. 2012. PMID: 23057966 Free PMC article. Review.
-
Acute myeloid leukemia: potential for new therapeutic approaches _targeting mRNA translation pathways.Int J Hematol Oncol. 2013 Jun;2(3):10.2217/ijh.13.23. doi: 10.2217/ijh.13.23. Int J Hematol Oncol. 2013. PMID: 24319589 Free PMC article.
-
Rapamycin sensitizes T-ALL cells to dexamethasone-induced apoptosis.J Exp Clin Cancer Res. 2010 Nov 18;29(1):150. doi: 10.1186/1756-9966-29-150. J Exp Clin Cancer Res. 2010. PMID: 21083937 Free PMC article.
-
Negative regulatory effects of Mnk kinases in the generation of chemotherapy-induced antileukemic responses.Mol Pharmacol. 2010 Oct;78(4):778-84. doi: 10.1124/mol.110.064642. Epub 2010 Jul 27. Mol Pharmacol. 2010. PMID: 20664001 Free PMC article.
-
Rapamycin restores p14, p15 and p57 expression and inhibits the mTOR/p70S6K pathway in acute lymphoblastic leukemia cells.Int J Hematol. 2015 Nov;102(5):558-68. doi: 10.1007/s12185-015-1858-1. Epub 2015 Sep 11. Int J Hematol. 2015. PMID: 26362858
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Research Materials
Miscellaneous