Omacetaxine as an Anticancer Therapeutic: What is Old is New Again

Author(s): Meir Wetzler, David Segal

Journal Name: Current Pharmaceutical Design

Volume 17 , Issue 1 , 2011


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Abstract:

Omacetaxine mepesuccinate was originally identified more than 35 years ago and initial studies in chronic myeloid leukemia (CML) showed promising activity. It has also been studied in other hematologic and solid tumors as both a single agent and in combination with other treatments. However, the introduction of imatinib and related tyrosine kinase inhibitors (TKIs) abated the clinical development of omacetaxine as a treatment for CML. The advent of resistance to imatinib and other TKIs in CML patients (often due to the presence of an ABL mutation at position 315) has led to a revived clinical interest in omacetaxine in CML patients who failed TKIs. Here we review omacetaxines mechanism of action (MOA) as a protein translation inhibitor, how its MOA may translate into activity in treatment of cancers, its potential to eradicate leukemia initiating cells and other cancer stem cells and the potential significance of this activity in clinical practice.

Keywords: Omacetacine, protein translation inhibition, chronic myeloid leukemia, leukemia initiating cells, cancer stem cells

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Article Details

VOLUME: 17
ISSUE: 1
Year: 2011
Published on: 01 March, 2012
Page: [59 - 64]
Pages: 6
DOI: 10.2174/138161211795049778

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