TUBB3 role in the response of tumor cells to epothilones and taxanes
Journal Title: Advances in Hygiene and Experimental Medicine - Year 2015, Vol 69, Issue 0
Abstract
Because of increased incidence of cancer and the development of resistance after treatment with typical drugs, new insights into the mechanisms of action of individual compounds are extremely valuable. In this article, we focus on taxanes, drugs belonging to the group of microtubule stabilizers, and their new generation - epothilones. Facing the fact that the molecular target for these compounds are microtubules, our attention was focused primarily on the role of overexpression of one of tubulin isotypes in response of tumor cells, particularly ovarian cancer to treatment with these compounds. On the basis of the literature data it can be concluded that one reason for the ineffectiveness of taxane is the resistance growing in the case of overexpression of b-tubulin class III- (TUBB3). Epothilones, however, due to their ability to bind equally to b-tubulin class I and III are effective in these cells, giving them an advantage over taxanes. It is necessary to emphasize the role of mikroRNA, transcription factors and other proteins associated with the activation of microtubules in development of resistance to taxanes and overcoming the resistance of the epothilones. Particularly interesting tubuseems to be the link between expression of TUBB3 and Glis proteins, which are end-effectors of Hedgehog pathway. Thanks to the confirmation that Gli1 overexpression is associated with decreased response to chemotherapy, it was possible to sensitize cells to epothilones after addition a suitable inhibitor.
Authors and Affiliations
Agnieszka Marczak, Aneta Rogalska
Keywords
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