© 1990 by Oxford University Press
Journal of the National Cancer Institute, Vol. 82, No. 15, 1247-1259,
August 1, 1990
© 1990 Oxford University Press
Taxol: A Novel Investigational Antimicrotubule Agent
American Cancer Society Career Development Award
Division of Pharmacology and Experimental Therapeutics, The Johns Hopkins Oncology Center Baltimore, Md
Investigational Drug Branch, Cancer Therapy and Evaluation Program, Division of Cancer Treatment, National Cancer Institute Bethesda, Md
*Correspondence to: Eric K. Rowinsky, M.D., Division of Pharmacology and Experimental Therapeutics, The Johns Hopkins Oncology Center, 600 N. Wolfe St., Baltimore, MD 21205.
Microtubules are among the most strategic subcellular targets of anticancer chemotherapeutics. Despite this fact, new antimicrotubule agents that possess unique mechanisms of cytotoxic action and have broader antineoplastic spectra than the vinca alkaloids have not been introduced over the last several decades—until the recent development of taxol. Unlike classical antimicrotubule agents like colchicine and the vinca alkaloids, which induce depolymerization of microtubules, taxol induces tubulin polymerization and forms extremely stable and nonfunctional microtubules. Taxol has demonstrated broad activity in preclinical screening studies, and antineoplastic activity has been observed in several classically refractory tumors. These tumors include cisplatin-resistant ovarian carcinoma in phase II trials and malignant melanoma and non-small cell lung carcinoma in phase I studies. Taxol's structural complexity has hampered the development of feasible processes for synthesis, and its extreme scarcity has limited the use of a conventional, broad-scale screening approach for evaluation of clinical antitumor activity. However, taxol's unique mechanism of action, its spectrum of preclinical antitumor activity, and tumor responses in early clinical trials have generated renewed interest in pursuing its development. [J Natl Cancer Inst 82: 1247–1259, 1990]
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