Abstract
Many of the cytotoxic drugs that are active in the curative or palliative treatment of human cancers are now known to mediate their effects through interaction with DNA topoisomerases stabilizing covalent DNA-protein intermediates. The epipodophylotoxins, anthracyclines, anthrapyrazoles, and actinomycins appear to target topoisomerase II, whereas drugs of the camptothecin class work specifically through their interaction with topoisomerase I. Some, such as actinomycin D, certain rebeccamycin analogs, and a new class of ethylidene glucoside-epipodophyllotoxins, may be dual-topoisomerase inhibitors (1). The clinical utility of the epipodophyllotoxin, etoposide, and the anthracyclines doxorubicin, daunorubicin, and actinomycin D have been well-established (2). The spectrum of utility of camptothecin drugs in treatment of human cancer also remains to be determined. However, current results from clinical trials suggest that drugs that target topoisomerase I may represent novel agents with considerable activity in a relatively broad spectrum of malignancies.
Keywords
- Proliferate Cell Nuclear Antigen
- Maximum Tolerate Dose
- Systemic Exposure
- Camptothecin Analog
- Intestinal Toxicity
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References
Trask DK, Muller MT. Stabilization of type I topoisomerase-DNA covalent complexes by actinomycin D. Proc Natl Acad Sci 1988; 85: 1417–1421.
Cancer Medicine, 4th ed. (Morton DL, Holland JF, Frei III E, Bast Jr RC, Kufe DU), Williams and Wilkins, Baltimore, Maryland, Weichselbaum, RR 1997.
Giovanella BC, Stehlin JS, Wall ME, Wani MC, Nicholas AW, Liu LF, et al. DNA topoisomerase 1-targeted chemotherapy of human colon cancer xenografts. Science 1989; 246: 1046–1048.
DeWys WD, Humphreys SR, Goldin A. Studies on the therapeutic effectiveness of drugs with tumor weight and survival time indices of Walker 256 carcinosarcoma. Cancer Chemo Rept 1968; 52 (2): 229–242.
Gallo RC, Whang-Peng J, Adamson RH. Studies on the antitumor activity, mechanism of action, and cell cycle effects of camptothecin. J Natl Cancer Inst 1971; 46: 789–795.
Gottlieb JA, Guarino AM, Call JB, Oliverio VT, Block JB. Preliminary pharmacologic and clinical evaluation of camptothecin sodium (NSC 100880). Cancer Chemother Rep 1970; 54: 461–470.
Moertel CG, Schutt AJ, Reitemeier RJ, Hahn RG. Phase II study of camptothecin (NSC-I00880) in the treatment of advanced gastrointestinal cancer. Cancer Chemother Rep 1972; 56: 95–101.
Kingsbury WD, Boehm JC, Jakas DR, Holden KG, Hecht SM, Gallagher G, et al. Synthesis of water soluble (aminoalkyl) camptothecin analogues: inhibition of topoisomerase I and antitumor activity. J Med Chem 1990; 4: 98–107.
Hsiang YH, Hertzberg R, Hecht S, Liu LE Camptothecin induces protein-linked DNA breaks via mammalian DNA topoisomerase I. J Biol Chem 1985; 260: 14873–14878.
Chen AY, Liu LF. DNA topoisomerases: essential enzymes and lethal targets Annu Rev Pharmacol Toxicol 1994; 34: 191–218.
Nitiss J, Wang JC. DNA topoisomerase-targeted drugs can be studied in yeast. Proc Natl Acad Sci USA 1988; 85: 7501–7505.
Liu LE Topoisomerase-I targeted drugs. Mechanism of inhibition and cytotoxicity. In: Taguchi T, Wang JC, eds. 5th World Conference on Clinical Pharmacology and Therapeutics. Highlights of a satellite symposium: Approaches to Cancer Treatment by Topoisomerase-I inhibitors. BIOMEDIS, Tokyo, 1992, pp. 6–9.
McCabe FL, Johnson RK. Comparative activity of oral and parenteral topotecan in murine tumor models: efficacy of oral topotecan. Cancer Investig 1994; 12: 308–313.
Kunimoto T, Nitta K, Tanaka T, Uehara N, Baba H, Takeuchi M, et al. Antitumor activity of 7-ethyl10-[4-(1-piperidino)-1-piperidino]-1-carbonyloxy-camptothecin, a novel water soluble derivative of camptothecin, against murine tumors. Cancer Res 1987; 47: 5944–5947.
Matsuzaki T, Yokokura T, Mutai M, Tsuruo T. Inhibition of spontaneous and experimental metastasis by a new derivative of camptothecin, irinotecan, in mice. Cancer Chemother Pharmacol 1988; 21: 308–312.
Bissery MC, Vrignaud P, Lavelle F, Chabot GG. Experimental antitumor activity and pharmacokinetics of the camptothecin analog irinotecan (CPT-11) Anti-Cancer Drugs 1996; 7: 437–460.
Kawato Y, Furuta T, Aonuma M, Yasuoka M, Yokokura T, Matsumoto K. Antitumor activity of a camptothecin derivative against human tumor xenografts in nude mice. Cancer Chemother Pharmacol 1991; 28: 192–198.
Pantazis P, Hinz HR, Mendoza JT, Kozielski AS, Williams LJ, Stehlin JS Jr., et al. Complete inhibition of growth followed by death of human malignant melanoma cells in vitro and regression of human melanoma xenografts in immunodeficient mice induced by camptothecins. Cancer Res 1992; 52: 3980–3987.
Houghton PJ, Cheshire PJ, Myers L, Stewart CF, Synold TW, Houghton JA. Evaluation of 9-dimethylaminomethyl- 10-hydroxycamptothecin against xenografts derived from adult and childhood solid tumors. Cancer Chemother Pharmacol 1992; 31: 229–239.
Pentazis P, Kozielski AJ, Verdeman DM, Petry ER, Giovanella BC. Efficacy of camptothecin congeners in the treatment of human breast carcinoma xenografts. Oncol Res 1993; 5: 273–281.
Houghton PJ, Cheshire PJ, Hallman JC, Bissery MC, Mathieu-Boue A, Houghton JA. Therapeutic efficacy of the topoisomerase I inhibitor 7-ethyl-10-(4-[1-piperidino]-1-piperidino)-carbonyloxy-camptothecin against human tumor xenografts: lack of cross resistance in vivo in tumors with acquired resistance to the topoisomerase inhibitor 9-dimethylaminomethy1-l0-hydoxycamptothecin. Cancer Res 1993; 53: 2823–2829.
Komuro H, Li P, Tsuchida Y, Yokomori K, Nakajima K, Aoyama T, et al. Effects of CPT11 (a unique DNA topoisomerase 1 inhibitor) on a highly malignant xeno-transplanted neuroblastoma. Med Pediatr Oncol 1994; 23: 487–492.
Houghton PJ, Cheshire PJ, Hallman JD, Lutz L, Friedman HS, Danks MK, et al. Efficacy of topoisomerase I inhibitors, topotecan and irinotecan, administered at low dose levels in protracted schedules to mice bearing xenografts of human tumors. Cancer Chemother Pharmacol 1995; 36: 393–403.
Emerson DL, Besterman JM, Brown HR, Evans MG, Leitner PP, Luzzio MJ, et al. In vivo antitumor activity of two seven-substituted water soluble camptothecin analogues. Cancer Res 1995; 55: 603–609.
Vassal G, Terrier-Lacombe MJ, Bissery MC, Venuat AM, Gyergyay F, Benard J, et al. Therapeutic activity of CPT-11, a DNA-topoisomerase I inhibitor, against peripheral primitive neuroectodermal tumour and neuroblastoma xenografts. Br J Cancer 1996; 74: 537–545.
Thompson J, Zamboni WC, Cheshire PJ, Lutz L, Luo X, Li Y, et al. Efficacy of systemic administration of irinotecan against neuroblastoma xenografts. Clin Cancer Res 1997; 3: 423–431.
Thompson J, Zamboni WC, Cheshire PJ, Richmond L, Luo X, Houghton JA, et al. Efficacy of oral administration of irinotecan against neuroblastoma xenografts. Anti-Cancer Drugs 1997; 8: 313–322.
Hare CB, Elion GB, Houghton PJ, Houghton JA, Keir S, Marcelli SL, et al. Therapeutic efficacy of the topoisomerase I inhibitor 7-ethyl-10-(4-[1-piperidino]-1-piperidino)-carbonyloxy-camptothecin against pediatric and adult central nervous system tumor xenografts. Cancer Chemother Pharmacol 1997; 393: 187–191.
deSouza PL, Cooper MR, Imondi AR, Myers CE. 9-aminocamptothecin: a topoisomerase I inhibitor with preclinical activity in prostate cancer. Clin Cancer Res 1997; 3:287–294. by 9-amino-20(S)camptothecin. Cancer Res 1997; 57: 1929–1933.
Zamboni WC, Stewart CF, Thompson J, Santana V, Cheshire PJ, Richmond LB, et al. The relationship between topotecan systemic exposure and tumor response in human neuroblastoma xenografts. J Natl Cancer Inst 1998; 90: 505–511.
Thompson J, Stewart CF, Houghton PJ. Animal models for studying the action of topoisomerase I targeted drug. Biochimica Biophysica Acta 1998; 1400: 301–319.
Furman WL, Stewart CF, Poquette CA, Pratt CB, Santana VM, Zamboni WC, et al. Direct translation of a protracted irinotecan schedule from xnograft model to phase I trial in chidren. J. Clin Oncol 1999; 17: 1815–1824.
Fujimori A, Harker WG, Kohlhagen G, Hold Y, Pommier Y. Mutation at the catalytic site of topoisomerase I in CEMIC2, a human leukemia cell line resistant to camptothecin. Cancer Res. 1995; 55: 1339–1346.
Knab AM, Fertala J, Bjornsti MA. A camptothecin-resistant DNA topoisomerase I mutant exhibits altered sensitivities to other DNA topoisomerase poisons. J Biol Chem 1995; 270: 6141–6148.
Houghton PJ, Stewart CF, Zamboni WC, Thompson J, Luo X, Danks MK, et al. Schedule-dependent efficacy of camptothecins in models of human cancer. Ann NYAcad Sci USA 1996; 803: 188–201.
Erickson-Miller CL, May RD, Tomaszewski J, Osborn B, Murphy MJ, Page JC, et al. Differential toxicity of camptothecin, topotecan and 9-aminocamptothecin to human, canine, and murine myeloid progenitors (CFU-GM) in vitro. Cancer Chemother Pharmacol 1997; 39: 467–472.
Wiseman LR, Markham A. Irinotecan. Drugs 1996; 52: 606–623.
Ikuno N, Soda H, Watanabe M, Oka M. Irinotecan (CPT-11) and characteristic mucosal changes in the mouse ileum and cecum. JNatl Cancer Inst 1995; 87: 1876–1883.
Shinohara H, Killion JJ, Kuniyasu H, Kumar R, Fidler IJ. Prevention of intestinal toxic effects and intensification of irinotecan’s thrapeutic efficacy against murine colon cancer liver metastases by oral administration of the lipopeptide JBT 3002. Clin Cancer Res 1998; 4: 2053–2063.
Sakai H, Diener M, Gartmann V, Takeguchi N. Eicosanoid-mediated Cl-secretion induced by the antitumor drug, irinotecan (CPT-11), in the rat. Naunyn-Schmiedeberg’s Arch Pharmacol 1995; 351: 309–314.
Takasuna K, Hagiwara T, Hirohashi M, Kato M, Nomura M, Nagai E, et al. Involvement of beta-glucoronidase in intestinal microflora in the intestinal toxicity of the antitumor camptothecin derivative irinotecan hydrochloride (CPT-11). Cancer Res 1996; 56: 3752–3757.
Cao S, Black JD, Troutt AB, Rustum YM. Interleukin 15 offers selective protection from irinotecaninduced intestinal toxicity in a preclinical animal model. Cancer Res 1998; 58: 3270–3274.
Bacon JA, Petrella DK, Cramer CT, Maruyama Y, Ford C, Stapert D, et al. Intestinal toxicity and changes in proliferating cell nuclear antigen (PCNA) levels in hamsters induced by a camptothecin analogue. The Toxicologist 1996; (abstract).
Kobayashi K, Bouscarel B, Matsuzaki Y, Ceryak S, Kudoh S, Fromm H. pH-dependent uptake of irinotecan and its active metabolite, SN-38, by intestinal cells. Int J Cancer 1999; 83: 491–496.
Roy SK, Clark DL, Zheng H, McGuinn WD, Smith DD, Andrews PA. Predictive value of rodent and non-rodent toxicology studies in support of phase I trials of topoisomerase inhibitors. 737A Proc American Assoc Cancer Res 1999; 40: 737A.
Stewart CF, Zamboni WC, Crom WR, Houghton Pi. Disposition of irinotecan and SN-38 following oral and intravenous irinotecan dosing in mice. Cancer Chemother Pharmacol 1997; 40: 259–265.
Abigerges D, Chabot GG, Armand J, Herait P, Gouyette A, Gandia D. Phase I and pharmacologic studies of the camptothecin analog irinotecan administered every three weeks in cancer patients. J Clin Oncol 1995; 13: 210–221.
Catimel G, Chabot GG, Guastalla JP, Dumortier A, Cote C, Engel C, et al. Phase I and pharmacokinetic study of irinotecan (CPT-11) administered daily for three consecutive days every three weeks in patients with advanced solid tumors. Annals Oncology 1995; 6 (2): 133–140.
Rothenberg ML, Kuhn JG, Burns HA, Nelson J, Eckardt JR, Tristan-Morales M, et al. Phase I and pharmacokinetic trial of weekly CPT-11. J Clin Oncol 1993; 11: 2194–2204.
Morton CL, Wierdl M, Oliver L, Ma M, Danks MK, Stewart CF, et al. Activation of CPT-11 in mice: identification and analysis of a highly effective plasma esterase, Cancer Res 2000; 60: 4206–4210.
Burke TG, Mi Z. The structural basis of camptothecin interactions with human serum albumin: impact on drug stability. J Med Chem 1994; 37: 40–46.
Burke TG, Munshi CB, Mi Z, Jiang Y. The important role of albumin in determining the relative human blood stabilities of the camptothecin anticancer drugs [letter] [published erratum appears] J Pharm Sci 1995; 84: 518–519.
Liehr JG, Ahmed AE, Giovanella BC. Pharmacokinetics of camptothecins administered orally. Ann NY Acad Sci 1996; 803: 157–163.
Daud SS, Fetouh MI, Giovanella BC. Antitumor effect of liposome-incorporated camptothecin in human malignant xenografts. Anti-Cancer Drugs 1995; 6: 83–93.
Burke TG, Gao X. Stabilization of topotecan in low pH liposomes composed of distearoylphosphatidylcholine. J Pharm Sci 1994; 83: 967–969.
Bailly C, Lansiaux A, Dassonneville L, Demarquay D, Coulomb H, Huchet M, et al. Homocamptothecin, an E-ring-modified camptothecin analogue, generates new topoisomerase I-mediated DNA breaks. Biochemistry 1999; 38:15, 556–15, 563.
Sanders MM, Liu AA, Li TK, Wu HY, Desai SD, Mao Y, et al. Selective cytotoxicity of topoisomerasedirected protoberberines against glioblastoma cells. Biochem Pharmacol 1998; 56: 1157–1166.
Bailly C, Qu X, Chaires JB, Colson P, Houssier C, Ohkubo M, et al. Substitution at the F-ring N-imide of the indolocarbazole antitumor drug NB-506 increases the cytotoxicity, DNA binding, and topoisomerase I inhibition activities. J Med Chem 1999; 42: 2927–2935.
Hill BT, Barrett JM, Perrin D, Gras S, Limouzy A, Chazottes E, et al. Mechanism of action of F 11782, a novel catalytic dual inhibitor of topoisomerase I and II. Proc Am Assoc Cancer Res 1999; 40: 755A.
Kruczynski A, Astruc J, Chazottes E, Ricome C, Berrichon G, Imbert T, et al. Preclinical antitumor activity of F 11782, a novel catalytic dual inhibitor of topoisomerase I and II. Proc Am Assoc Cancer Res 1999; 40: 757A.
Kobayashi K, Takeda Y, Akiyama Y, Soma T, Hand T, Kudo K, et al. Reduced irinotecan-induced side-effects by the oral alkalinization. Proc Am Assoc Clin Oncol 1999; 18: 1900a.
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Thompson, J., Stewart, C.F., Houghton, P.J. (2002). Models for Studying the Action of Topoisomerase-I Targeted Drugs. In: Teicher, B.A. (eds) Tumor Models in Cancer Research. Cancer Drug Discovery and Development. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-100-8_29
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DOI: https://doi.org/10.1007/978-1-59259-100-8_29
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