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Current Cancer Drug Targets


ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

Looking at Drug Resistance Mechanisms for Microtubule Interacting Drugs: Does TUBB3 Work?

Author(s): Cristiano Ferlini, Giuseppina Raspaglio, Lucia Cicchillitti, Simona Mozzetti, Silvia Prislei, Silvia Bartollino and Giovanni Scambia

Volume 7, Issue 8, 2007

Page: [704 - 712] Pages: 9

DOI: 10.2174/156800907783220453

Price: $65


Vinca alkaloids and taxanes represent the mainstay of medical treatment of hematological and solid tumors. Unfortunately, a major clinical problem with these agents is drug resistance. Although a plethora of mechanisms of drug resistance have been described, only a few of them have been validated in clinical trials. Among these, the one involving the protein TUBB3 seems to represent a promising target for studying drug resistance. In fact, it seems that this protein is a factor promoting cell survival and represents an endogenous element of an inherent drug-resistance program built into cells to counteract the activity of microtubule-interacting drugs. Its pivotal role has been ascertained in clinical trials in lung, breast, and ovarian cancer, three diseases that can be successfully treated with microtubule-interacting drugs. Although TUBB3 is probably not a unique factor in drug resistance, the hope is that direct targeting of this protein will increase the response to microtubule-interacting drugs, thereby overcoming an important element in the growth of drug resistance.

Keywords: TUBB3, tubulin, drug resistance, taxanes, vinca alkaloids, ovarian cancer, lung cancer

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