Homoharringtonine, omacetaxine mepesuccinate, and chronic myeloid leukemia circa 2009.

Abstract

Homoharringtonine (HHT) is a natural alkaloid that is obtained from various Cephalotaxus species. The mechanism of action by which HHT exerts its antitumor activity is through inhibition of protein synthesis and promotion of apoptosis. In the 1990s, HHT proved to be significantly active as salvage therapy for patients with chronic myeloid leukemia (CML) after failure on interferon-alpha therapy. However, the remarkable success of imatinib mesylate in the treatment of CML relegated HHT to oblivion. The development of omacetaxine mepesuccinate, a subcutaneously bioavailable semisynthetic form of HHT, and its activity in imatinib-resistant CML has established this agent for the second time as a valuable option in the management of this disease. Preliminary results appear to support the use of this agent for patients who have imatinib-resistant CML, including those who carry the tyrosine kinase inhibitor-insensitive mutation that exchanges the amino acids threonine and isoleucine at position 315 (the T315I mutation). In this article, the authors discuss the current data on omacetaxine and the prospects of this agent to be integrated into the state-of-the-art treatment algorithms for CML.

• Authors: Alfonso Quintás-Cardama, Hagop Kantarjian, Jorge Cortes
• Journal: Cancer (Cancer) Vol. 115 Issue 23 Pg. 5382-93 (Dec 01 2009) ISSN: 0008-543X [Print] United States
• PMID: 19739234 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: (c) 2009 American Cancer Society.

Chemical References

• Antineoplastic Agents, Phytogenic
• Benzamides
• Harringtonines
• Piperazines
• Pyrimidines
• Homoharringtonine
• Imatinib Mesylate

Topics

• Algorithms
• Antineoplastic Agents, Phytogenic (therapeutic use)
• Benzamides
• Clinical Trials as Topic
• Drug Discovery
• Drug Resistance, Neoplasm
• Drug Screening Assays, Antitumor
• Harringtonines (chemistry, therapeutic use)
• Homoharringtonine
• Humans
• Imatinib Mesylate
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive (drug therapy, genetics)
• Piperazines (therapeutic use)
• Pyrimidines (therapeutic use)