Zusammenfassung
Paclitaxel, docetaxel and vinca alkaloids like vinblastine are compounds interacting with the mitotic spindle by binding to beta-tubulin. They are used as therapeutics in standard chemotherapy regimens an in combination with new drugs like the HER2 targeting antibody trastuzumab. But toxicity, drug resistance, complex galenic formulations and limited bioavailability are restricting their clinical ...
Zusammenfassung
Paclitaxel, docetaxel and vinca alkaloids like vinblastine are compounds interacting with the mitotic spindle by binding to beta-tubulin. They are used as therapeutics in standard chemotherapy regimens an in combination with new drugs like the HER2 targeting antibody trastuzumab. But toxicity, drug resistance, complex galenic formulations and limited bioavailability are restricting their clinical use in cancer therapy. Thus, new tubulin targeting antimitotic agents with better tolerability and efficacy against late-stage resistant tumors are urgently needed. This review summarizes tubulin targeting drugs in late preclinical and early clinical development, as well as compounds with interesting structural features. Pharmacological and clinical phase I/II data are presented for new semisynthetic paclitaxel analogues and natural compounds of diverse structure such as epothilones, combretastatins, colchinoids or dolastatins. Finally, synthetic compounds of low molecular weight but cytotoxic activity equal to paclitaxel are presented. With a clear focus on clinical efficacy and superiority to current antimitotic agents, this timely review attempts to give a perspective on the progress of an important class of anticancer drugs.
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