Editorial [Hot Topic: Tubulin/Microtubule System as an Anti-Cancer Drug Target (Guest Editor: A/Prof. Maria Kavallaris Ph.D.) ]

Publisher： Bentham Science Publishers

E-ISSN： 1873-5576|7|8|696-696

ISSN： 1568-0096

Source： Current Cancer Drug Targets, Vol.7, Iss.8, 2007-12, pp. : 696-696

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Abstract

The tubulin/microtubule system is an integral component of the cytoskeleton. Microtubules are highly dynamic structures that play a critical role in orchestrating the separation and segregation of chromosomes during mitosis. This makes microtubules highly valued as anticancer drug targets. Tubulin-binding agents (also known as anti-microtubule, microtubule-binding, microtubule-targeting drugs) are derived from natural sources and include a large number of agents with diverse chemical structures. What all tubulin-binding agents share in common is their ability to disrupt microtubule dynamics, induce mitotic arrest and cell death. The best known of these agents are the vinca alkaloids and taxanes, which at high doses cause microtubule destabilisation and microtubule stabilisation, respectively.Improvements in our understanding of the mechanisms of action and resistant to tubulin-binding agents has continued to drive a strong interest in identifying and developing new derivatives of tubulin-binding agents. Well over 200 of these agents are under various stages of development. Despite the fact that the first tubulin-binding agents, were clinically introduced in the 1960's, there are still many aspects of these agents that are not understood and in recent years, previously unknown cellular effects and protein interactions have begun to be discovered.It has been known for some time that tubulin-binding agents disrupt microtubule dynamics, but the differences between the different classes of tubulin-binding agents and their effects on microtubule dynamics and mitosis have been difficult to pinpoint. Jordan and Kamath give a valuable overview of microtubule dynamics, endogenous regulators of microtubule function and the effect of different classes of tubulin-binding agents on microtubule dynamics.The role of microtubule binding proteins in the regulation of microtubule dynamics and drug response have been studied, yet limited attention has been given to the role of tubulin folding pathways as a means to regulate microtubule dynamics. Beghin, Galmarini and Dumontet, review current understanding regarding tubulin-folding pathways, their relation to disease, and discuss their potential influence on microtubule dynamics and their value as new drug targets.Despite the clinical success of tubulin-binding agents, drug resistance can emerge as a significant clinical problem. There has been much interest in recent years associated with alterations in the cellular target of these agents, the tubulin/microtubule system. The mechanisms mediating resistance in the clinic are not well understood. Ferlini et al. review resistance mechanisms and discuss the benefits of targeting TUBB3 (also known as class III &bgr;-tubulin or &bgr;III-tubulin), a &bgr;-tubulin isotype commonly increased in drug resistant epithelial cancers.Tubulin-binding agents are known to be potent inducers of apoptosis. The link between microtubule disruption and apoptosis induction are not clear. Esteve, Carre and Braguer give a comprehensive overview of the apoptotic processes known to be activated following treatment of cancer cells with tubulin-binding agents.The tubulin/microtubule system remains one the most important drug targets for the treatment of cancer. This special issue provides current and new insight into the mechanisms of action of these agents, resistance and new drug targets within the tubulin/microtubule repertoire of microtubule dynamic regulators. Improved insight into the mechanisms of action and resistance to these agents will lead to improved targeting of existing agents and the development of more effective agents to treat resistant disease.