Camptothecin and taxol: historic achievements in natural products research.
The research team of Dr. Monroe E. Wall and Dr. Mansukh C. Wani of Research Triangle Institute discovered two first-in-class life-saving chemotherapeutic agents. Camptothecin, first isolated and identified from Camptotheca acuminata, was found to kill cancer cells uniquely via topoisomerase I poisoning. Presently, two first-generation analogues of camptothecin are used to treat ovarian, colorectal, and small-cell lung cancers, and several second-generation analogues are in clinical trials. Taxol, first isolated and identified by Wall and Wani from Taxus brevifolia, was found to inhibit cancer cell growth via the stabilization of microtubules. In 1992, taxol was approved for refractory ovarian cancer and today is used against breast and non-small cell lung cancers and in Kaposi's sarcoma. While there have been numerous reviews of these molecules individually, this review offers an integrated account of the research team of "Wall and Wani" and the significance of their discoveries to chemistry, biology, and clinical medicine.
Oberlies
Nicholas H
NH
Natural Products Laboratory, Research Triangle Institute, P.O. Box 12194, Research Triangle Park, North Carolina 27709-2194, USA. oberlies@rti.org
Kroll
David J
DJ
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000266:history* / Q000494:pharmacology; D001688:Biological Products / Q000737:chemistry / Q000266:history* / Q000494:pharmacology; D029769:Camptotheca / Q000737:chemistry; D002166:Camptothecin / Q000737:chemistry / Q000266:history* / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000266:history; D049673:History, 20th Century; D006801:Humans; D017239:Paclitaxel / Q000737:chemistry / Q000266:history* / Q000494:pharmacology; D020946:Taxus / Q000737:chemistry; D059004:Topoisomerase I Inhibitors
D000972:Antineoplastic Agents, Phytogenic; D001688:Biological Products; D004791:Enzyme Inhibitors; D059004:Topoisomerase I Inhibitors; D017239:Paclitaxel; D002166:Camptothecin