Tyrosine Kinase Inhibitors for the Treatment of Chronic Myeloid Leukemia

ISSN: 1875-5992 (Online)
ISSN: 1871-5206 (Print)


Volume 16, 12 Issues, 2016


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Anti-Cancer Agents in Medicinal Chemistry

Formerly: Current Medicinal Chemistry - Anti-Cancer Agents

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Editor-in-Chief:
Michelle Prudhomme
Universite Blaise Pascal - C.N.R.S
Aubiere Cedex
France


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Tyrosine Kinase Inhibitors for the Treatment of Chronic Myeloid Leukemia



Anti-Cancer Agents in Medicinal Chemistry, 9(8): 853-863.

Author(s): Manlio Tolomeo, Francesco Dieli, Nicola Gebbia and Daniele Simoni.

Affiliation: Centro Interdipartimentale di Ricerca in Oncologia Clinica, Policlinico “P. Giaccone”, Universita di Palermo, 90127, Italy.

Abstract

Imatinib mesylate (Gleevec) is a drug unique for the treatment of certain forms of cancer. It works by targeting, and turning off, specific tyrosine kinase proteins that cause the uncontrolled cell growth and the inhibition of apoptosis in cancer cells. Imatinib was designed on the basis of the structure of the ATP binding site of the Abl protein kinase with the aim to stabilize the inactive form of Bcr-Abl, an oncoprotein involved in malignant transformation in chronic myelogenous leukemia (CML). However, imatinib can also target other tyrosine kinase proteins different from Bcr-Abl such as Kit, that is the suspected cause of gastrointestinal stromal tumor (GIST). Despite successful clinical results observed in the last years, the long-term effects of imatinib and its ability to completely eradicate CML are still unknown. Moreover, similar to many other anti-cancer drugs, clinical resistance to imatinib has emerged. In this review we will discuss the in vitro and in vivo results obtained with the novel tyrosine kinase inhibitors developed to overcome imatinib resistance in Bcr-Abl expressing hematologiocal disorders.

Keywords:

Bcr-Abl, chronic myelogenous leukemia, tyrosine kinase inhibitors.



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Article Details

Volume: 9
Issue Number: 8
First Page: 853
Last Page: 863
Page Count: 11
DOI: 10.2174/187152009789124637
Price: $58
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