The cytoskeleton as a therapeutic target in childhood acute leukemia: obstacles and opportunities.

Abstract

Antimitotic agents that interfere with the tubulin/microtubule system are important in the treatment of a range of cancers. Natural product tubulin-binding agents such as the Vinca alkaloids have proven highly effective in the treatment of leukemia. Improved understanding of the mechanisms of action of these and related drugs has led to the identification of distinct binding sites on tubulin that cause inhibition of spindle microtubule dynamics, mitotic arrest and cell death. Despite the efficacy of these agents, treatment failure caused by the emergence of drug resistant leukemic cells is a significant clinical problem. Alterations in the cellular target of tubulin-binding agents have been strongly implicated in resistance to these agents. This review will focus on the microtubule cytoskeleton and its role in drug resistance in leukemia. The identification of novel protein pathways involved in drug response and the development of new drugs targeted against microtubules, offers opportunities to treat resistant disease, improve outcome and potentially reduce toxicity for leukemia patients.

• Authors: Tracy Y E Liaw, Melissa H Y Chang, Maria Kavallaris
• Journal: Current drug targets (Curr Drug Targets) Vol. 8 Issue 6 Pg. 739-49 (Jun 2007) ISSN: 1873-5592 [Electronic] United Arab Emirates
• PMID: 17584029 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Antineoplastic Agents
• Tubulin
• Tubulin Modulators
• Vinca Alkaloids

Topics

• Acute Disease
• Antineoplastic Agents (pharmacology, therapeutic use)
• Child
• Drug Delivery Systems
• Drug Resistance, Neoplasm
• Humans
• Leukemia (drug therapy, pathology)
• Microtubules (drug effects, pathology)
• Tubulin (drug effects)
• Tubulin Modulators (pharmacology, therapeutic use)
• Vinca Alkaloids (pharmacology, therapeutic use)