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Topoisomerase I Inhibitors – The Camptothecins

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Cancer Management in Man: Chemotherapy, Biological Therapy, Hyperthermia and Supporting Measures

Part of the book series: Cancer Growth and Progression ((CAGP,volume 13))

Abstract

The camptothecins are a class of antineoplastic agents that inhibit the enzyme DNA topoisomerase I and have established activity in the treatment of various human malignancies. Camptothecin (CPT) was originally isolated in 1966 from the bark and stem of the native Chinese tree, Campotheca acuminate [155]. Although camptothecin demonstrated promising antitumor effects in animal systems, its utility was compromised in the clinical setting because of erratic absorption, insolubility, and severe toxicities. However, interest was renewed in the mid-1980s when the topoisomerase enzyme was identified as the cellular target of camptothecin. This led to the development of more soluble and less toxic camptothecin analogs with even greater preclinical anticancer activity, including the two FDA approved agents, irinotecan and topotecan. There are several other campothecin analogs in various stages of clinical investigation including SN-38, 9-aminocamptothecin (9-AC), 9-Nitrocamptothecin (9-NC), lurtotecan (GI-47211), rubitecan, OSI-211, exatecan mesylate (DX8951f), diflomotecan (BN80915), gimatecan (ST1481), CKD-602, DB-67, and karenitecin (BNP1350). The advancement of these agents and further development within the class may further signify the importance of topoisomerase I inhibition as a major target for cancer chemotherapy [105].

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Authors and Affiliations

  1. Department of Clinical Pharmacy, West Virginia University School of Pharmacy and Mary Babb Randolph Cancer Center, Morgantown, WV, 26506, USA

    Michael Newton

  2. Malignant Hematology Program and Department of Pharmacy, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USA

    Gene Wetzstein

  3. Experimental Therapeutics Program and Department of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USA

    Daniel Sullivan

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  1. Michael Newton
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  3. Daniel Sullivan
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Correspondence to Daniel Sullivan .

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  1. Moores UCSD Cancer Center, 3855 Health Sciences Drive 0820, La Jolla, 92093-0820, California, USA

    Boris R. Minev

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Newton, M., Wetzstein, G., Sullivan, D. (2011). Topoisomerase I Inhibitors – The Camptothecins. In: Minev, B. (eds) Cancer Management in Man: Chemotherapy, Biological Therapy, Hyperthermia and Supporting Measures. Cancer Growth and Progression, vol 13. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-9704-0_6

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