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Imatinib mesylate potentiates topotecan antitumor activity in rhabdomyosarcoma preclinical models

  1. Heather P. McDowell1,2,†,‡,*,
  2. Daniela Meco2,†,
  3. Anna Riccardi2,
  4. Barbara Tanno3,
  5. Anna C. Berardi4,
  6. Giuseppe Raschellà3,
  7. Riccardo Riccardi2,
  8. Carlo Dominici5,6,7

Article first published online: 27 NOV 2006

DOI: 10.1002/ijc.22391

Issue

International Journal of Cancer

International Journal of Cancer

Volume 120, Issue 5, pages 1141–1149, 1 March 2007

Additional Information

How to Cite

McDowell, H. P., Meco, D., Riccardi, A., Tanno, B., Berardi, A. C., Raschellà, G., Riccardi, R. and Dominici, C. (2007), Imatinib mesylate potentiates topotecan antitumor activity in rhabdomyosarcoma preclinical models. Int. J. Cancer, 120: 1141–1149. doi: 10.1002/ijc.22391

Author Information

  1. 1

    Department of Oncology, Royal Liverpool Children's NHS Trust Alder Hey, Liverpool, United Kingdom

  2. 2

    Department of Paediatrics, Catholic University, Rome, Italy

  3. 3

    Section of Toxicology and Biomedical Sciences, ENEA Research Center Casaccia, Rome, Italy

  4. 4

    Laboratory of Stem Cells, Bambino Gesù Children's Hospital, Rome, Italy

  5. 5

    Laboratory of Oncology, Bambino Gesù Children's Hospital, Rome, Italy

  6. 6

    Department of Paediatrics, La Sapienza University, Rome, Italy

  7. 7

    Division of Child Health, School of Reproductive and Developmental Medicine, Liverpool University, Liverpool, United Kingdom

  1. †

    The first two authors contributed equally to this work.

  2. ‡

    Fax: +44-151-252-5676.

*Department of Oncology, Royal Liverpool Children's NHS Trust Alder Hey, Eaton Road, Liverpool L12 2AP, UK

Publication History

  1. Issue published online: 19 JAN 2007
  2. Article first published online: 27 NOV 2006
  3. Manuscript Accepted: 29 AUG 2006
  4. Manuscript Received: 28 APR 2006

Funded by

  • Italian Ministry of Health. Grant Number: 212/2003
  • “Fondazione per l'Oncologia Pediatrica”
  • “Io…domani” Associazione per la Lotta contro i Tumori Infantili (ALTI)

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References

  • 1
    Buchdunger E, O'Reilly T, Wood J. Pharmacology of imatinib (STI571). Eur J Cancer 2002; 38: 28–36.
  • 2
    Deininger M, Buchdunger E, Druker BJ. The development of imatinib as a therapeutic agent for chronic myeloid leukemia. Blood 2005; 105: 2640–53.
  • 3
    Dewar AL, Cambareri AC, Zannettino AC, Miller BL, Doherty KV, Hughes TP, Lyons AB. Macrophage colony-stimulating factor receptor c-fms is a novel target of imatinib. Blood 2005; 105: 3127–32.
  • 4
    Druker BJ, Talpaz M, Resta DJ, Peng B, Buchdunger E, Ford JM, Lydon NB, Kantarjian H, Capdeville R, Ohno-Jones S, Sawyers CL. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med. 2001; 344: 1031–7.
  • 5
    Demetri GD, von Mehren M, Blanke CD, Van den Abbeele AD, Eisenberg B, Roberts PJ, Heinrich MC, Tuveson DA, Singer S, Janicek M, Fletcher JA, Silverman SG et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med 2002; 347: 472–80.
  • 6
    Wang WL, Healy ME, Sattler M, Verma S, Lin J, Maulik G, Stiles CD, Griffin JD, Johnson BE, Salgia R. Growth inhibition and modulation of kinase pathways of small cell lung cancer cell lines by the novel tyrosine kinase inhibitor STI 571. Oncogene 2000; 19: 3521–8.
  • 7
    Kilic T, Alberta JA, Zdunek PR, Acar M, Iannarelli P, O'Reilly T, Buchdunger E, Black PM, Stiles CD. Intracranial inhibition of platelet-derived growth factor-mediated glioblastoma cell growth by an orally active kinase inhibitor of the 2-phenylaminopyrimidine class. Cancer Res 2000; 60: 5143–50.
  • 8
    Attoub S, Rivat C, Rodrigues S, Van Bocxlaer S, Bedin M, Bruyneel E, Louvet C, Kornprobst M, Andre T, Mareel M, Mester J, Gespach C. The c-kit tyrosine kinase inhibitor STI571 for colorectal cancer therapy. Cancer Res 2002; 62: 4879–83.
  • 9
    Merchant MS, Woo CW, Mackall CL, Thiele CJ. Potential use of imatinib in Ewings sarcoma: evidence for in vitro and in vivo activity. J Natl Cancer Inst 2002; 94: 1673–9.
  • 10
    Vitali R, Cesi V, Nicotra MR, McDowell HP, Donfrancesco A, Mannarino O, Natali PG, Raschellà G, Dominici C. c-Kit is preferentially expressed in MYCN-amplified neuroblastoma and its effect on cell proliferation is inhibited in vitro by STI-571. Int J Cancer 2003; 106: 147–52.
    Direct Link:
  • 11
    Beppu K, Jaboine J, Merchant MS, Mackall CL, Thiele CJ. Effect of imatinib mesylate on neuroblastoma tumorigenesis and vascular endothelial growth factor expression. J Natl Cancer Inst 2004; 96: 46–55.
  • 12
    Meco D, Riccardi A, Servidei T, Brueggen J, Gessi M, Riccardi R, Dominici C. Antitumor activity of imatinib mesylate in neuroblastoma xenografts. Cancer Lett 2005; 228: 211–19.
  • 13
    Houghton PJ, Germain GS, Harwood FC, Schuetz JD, Stewart CF, Buchdunger E, Traxler P. Imatinib mesylate is a potent inhibitor of the ABCG2 (BCRP) transporter and reverses resistance to topotecan and SN-38 in vitro. Cancer Res 2004; 64: 2333–7.
  • 14
    Ozvegy-Laczka C, Hegedus T, Varady G, Ujhelly O, Schuetz JD, Varadi A, Keri G, Orfi L, Nemet K, Sarkadi B. High-affinity interaction of tyrosine kinase inhibitors with the ABCG2 multidrug transporter. Mol Pharmacol 2004; 65: 1485–95.
  • 15
    Haimeur A, Conseil G, Deeley RG, Cole SP. The MRP-related and BCRP/ABCG2 multidrug resistance proteins: biology, substrate specificity and regulation. Curr Drug Metab 2004; 5: 21–53.
  • 16
    Breitfeld PP, Lyden E, Raney RB, Teot LA, Wharam M, Lobe T, Crist WM, Maurer HM, Donaldson SS, Ruymann FB. Ifosfamide and etoposide are superior to vincristine and melphalan for pediatric metastatic rhabdomyosarcoma when administered with irradiation and combination chemotherapy: a report from the Intergroup Rhabdomyosarcoma Study Group. J Pediatr Hematol Oncol 2001; 23: 225–33.
  • 17
    Crist WM, Anderson JR, Meza JL, Fryer C, Raney RB, Ruymann FB, Breneman J, Qualman SJ, Wiener E, Wharam M, Lobe T, Webber B et al. Intergroup Rhabdomyosarcoma Study. IV. Results for patients with nonmetastatic disease. J Clin Oncol 2001; 19: 3091–102.
  • 18
    Pappo AS, Shapiro DN, Crist WM, Maurer HM. Biology and therapy of pediatric rhabdomyosarcoma. J Clin Oncol 1995; 13: 2123–39.
  • 19
    Anderson J, Gordon T, McManus A, Mapp T, Gould S, Kelsey A, McDowell H, Pinkerton R, Shipley J, Pritchard-Jones K. Detection of the PAX3-FKHR fusion gene in paediatric rhabdomyosarcoma: a reproducible predictor of outcome? Br J Cancer 2001; 85: 831–5.
  • 20
    Sorensen PH, Lynch JC, Qualman SJ, Tirabosco R, Lim JF, Maurer HM, Bridge JA, Crist WM, Triche TJ, Barr FG. PAX3-FKHR and PAX7-FKHR gene fusions are prognostic indicators in alveolar rhabdomyosarcoma: a report from the Children's Oncology Group. J Clin Oncol 2002; 20: 2672–9.
  • 21
    Weigel BJ, Breitfeld PP, Hawkins D, Crist WM, Baker KS. Role of high-dose chemotherapy with hematopoietic stem cell rescue in the treatment of metastatic or recurrent rhabdomyosarcoma. J Pediatr Hematol Oncol 2001; 23: 272–6.
  • 22
    Blandford MC, Barr FG, Lynch JC, Lor Randall R, Qualman SJ, Keller C. Rhabdomyosarcomas utilize developmental, myogenic growth factors for disease advantage: A report from the Children's Oncology Group. Pediatr Blood Cancer 2006; 46: 329–38.
    Direct Link:
  • 23
    Smithey BE, Pappo AS, Hill DA. c-kit expression in pediatric solid tumors: a comparative immunohistochemical study. Am J Surg Pathol 2002; 26: 486–92.
  • 24
    Pappo AS, Lyden E, Breneman J, Wiener E, Teot L, Meza J, Crist W, Vietti T. Up-front window trial of topotecan in previously untreated children and adolescents with metastatic rhabdomyosarcoma: an Intergroup Rhabdomyosarcoma Study. J Clin Oncol 2001; 19: 213–19.
  • 25
    Houghton JA, Houghton PJ, Brodeur GM, Green AA. Development of resistance to vincristine in a childhood rhabdomyosarcoma growing in immune-deprived mice. Int J Cancer 1981; 28: 409–15.
    Direct Link:
  • 26
    Nanni P, Schiaffino S, De Giovanni C, Nicoletti G, Prodi G, Del Re B, Eusebi V, Ceccarelli C, Saggin L, Lollini PL. RMZ: a new cell line from a human alveolar rhabdomyosarcoma. In vitro expression of embryonic myosin. Br J Cancer 1986; 54: 1009–114.
  • 27
    Douglass EC, Valentine M, Etcubanas E, Parham D, Webber BL, Houghton PJ, Houghton JA, Green AA. A specific chromosomal abnormality in rhabdomyosarcoma. Cytogenet Cell Genet 1987; 45: 148–55.
  • 28
    De Giovanni C, Nanni P, Nicoletti G, Ceccarelli C, Scotlandi K, Landuzzi L, Lollini PL. Metastatic ability and differentiative properties of a new cell line of human embryonal rhabdomyosarcoma (CCA). Anticancer Res 1989; 9: 1943–9.
  • 29
    Lollini PL, De Giovanni C, Landuzzi L, Nicoletti G, Scotlandi K, Nanni P. Reduced metastatic ability of in vitro differentiated human rhabdomyosarcoma cells. Invasion Metastasis 1991; 11: 116–24.
  • 30
    Matsushima H, Bogenmann E. Bi-modal differentiation pattern in a new human neuroblastoma cell line in vitro. Int J Cancer 1992; 51: 250–8.
    Direct Link:
  • 31
    Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 1983; 65: 55–63.
  • 32
    Chou TC, Talalay P. Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul 1984; 22: 27–55.
  • 33
    Tanno B, Negroni A, Vitali R, Pirozzoli MC, Cesi V, Mancini C, Calabretta B, Raschellà G. Expression of insulin-like growth factor-binding protein 5 in neuroblastoma cells is regulated at the transcriptional level by c-Myb and B-Myb via direct and indirect mechanisms. J Biol Chem 2002; 277: 23172–80.
  • 34
    Ozvegy C, Varadi A, Sarkadi B. Characterization of drug transport, ATP hydrolysis, and nucleotide trapping by the human ABCG2 multidrug transporter. Modulation of substrate specificity by a point mutation. J Biol Chem 2002; 277: 47980–90.
  • 35
    Allen JD, van Loevezijn A, Lakhai JM, van der Valk M, van Tellingen O, Reid G, Schellens JH, Koomen GJ, Schinkel AH. Potent and specific inhibition of the breast cancer resistance protein multidrug transporter in vitro and in mouse intestine by a novel analogue of fumitremorgin C. Mol Cancer Ther 2002; 1: 417–25.
  • 36
    Robinson DR, Wu YM, Lin SF. The protein tyrosine kinase family of the human genome. Oncogene 2000; 19: 5548–57.
  • 37
    Bennasroune A, Gardin A, Aunis D, Crémel G, Hubert P. Tyrosine kinase receptors as attractive targets of cancer therapy. Crit Rev Oncol Hematol 2004; 50: 23–38.
  • 38
    Schmidt L, Duh FM, Chen F, Kishida T, Glenn G, Choyke P, Scherer SW, Zhuang Z, Lubensky I, Dean M, Allikmets R, Chidambaram A, et al. Germline and somatic mutations in the tyrosine kinase domain of the MET proto-oncogene in papillary renal carcinomas. Nat Genet 1997; 16: 68–73.
  • 39
    Park WS, Dong SM, Kim SY, Na EY, Shin MS, Pi JH, Kim BJ, Bae JH, Hong YK, Lee KS, Lee SH, Yoo NJ et al. Somatic mutations in the kinase domain of the Met/hepatocyte growth factor receptor gene in childhood hepatocellular carcinomas. Cancer Res 1999; 59: 307–10.
  • 40
    Ma PC, Kijima T, Maulik G, Fox EA, Sattler M, Griffin JD, Johnson BE, Salgia R. c-MET mutational analysis in small cell lung cancer: novel juxtamembrane domain mutations regulating cytoskeletal functions. Cancer Res 2003; 63: 6272–81.
  • 41
    Hirota S, Isozaki K, Moriyama Y, Hashimoto K, Nishida T, Ishiguro S, Kawano K, Hanada M, Kurata A, Takeda M, Muhammad Tunio G, Matsuzawa Y et al. Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science 1998; 279: 577–80.
  • 42
    Rubin BP, Singer S, Tsao C, Duensing A, Lux ML, Ruiz R, Hibbard MK, Chen CJ, Xiao S, Tuveson DA, Demetri GD, Fletcher CD et al. KIT activation is a ubiquitous feature of gastrointestinal stromal tumors. Cancer Res 2001; 61: 8118–21.
  • 43
    Kemmer K, Corless CL, Fletcher JA, McGreevey L, Haley A, Griffith D, Cummings OW, Wait C, Town A, Heinrich MC. KIT mutations are common in testicular seminomas. Am J Pathol 2004; 164: 305–13.
  • 44
    Boldrini L, Ursino S, Gisfredi S, Faviana P, Donati V, Camacci T, Lucchi M, Mussi A, Basolo F, Pingitore R, Fontanini G. Expression and mutational status of c-kit in small-cell lung cancer: prognostic relevance. Clin Cancer Res 2004; 10: 4101–8.
  • 45
    Willmore-Payne C, Holden JA, Tripp S, Layfield LJ. Human malignant melanoma: detection of BRAF- and c-kit-activating mutations by high-resolution amplicon melting analysis. Hum Pathol 2005; 36: 486–93.
  • 46
    Cappellen D, De Oliveira C, Ricol D, de Medina S, Bourdin J, Sastre-Garau X, Chopin D, Thiery JP, Radvanyi F. Frequent activating mutations of FGFR3 in human bladder and cervix carcinomas. Nat Genet 1999; 23: 18–20.
  • 47
    Bakkar AA, Wallerand H, Radvanyi F, Lahaye JB, Pissard S, Lecerf L, Kouyoumdjian JC, Abbou CC, Pairon JC, Jaurand MC, Thiery JP, Chopin DK et al. FGFR3 and TP53 gene mutations define two distinct pathways in urothelial cell carcinoma of the bladder. Cancer Res 2003; 63: 8108–12.
  • 48
    Zhang Y, Hiraishi Y, Wang H, Sumi KS, Hayashido Y, Toratani S, Kan M, Sato JD, Okamoto T. Constitutive activating mutation of the FGFR3b in oral squamous cell carcinomas. Int J Cancer 2005; 117: 166–8.
    Direct Link:
  • 49
    Heinrich MC, Corless CL, Duensing A, McGreevey L, Chen CJ, Joseph N, Singer S, Griffith DJ, Haley A, Town A, Demetri GD, Fletcher CD et al. PDGFRA activating mutations in gastrointestinal stromal tumors. Science 2003; 299: 708–10.
  • 50
    Frederick L, Wang XY, Eley G, James CD. Diversity and frequency of epidermal growth factor receptor mutations in human glioblastomas. Cancer Res 2000; 60: 1383–7.
  • 51
    Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, Harris PL, Haserlat SM, Supko JG, Haluska FG, Louis DN, Christiani DC et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 2004; 350: 2129–39.
  • 52
    Paez JC, Jänne PA, Lee JC, Tracy S, Greulich H, Gabriel S, Herman P, Kaye FJ, Lindeman N, Boggon TJ, Naok K, Sasaki H et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 2004; 304: 1497–1500.
  • 53
    Pao W, Miller V, Zakowski M, Doherty J, Politi K, Sarkaria I, Singh B, Heelan R, Rusch V, Fulton L, Mardis E, Kupfer D et al. EGF receptor gene mutations are common in lung cancers from never smokers and are associated with sensitivity of tumors to gefitinib and erlotinib. Proc Natl Acad Sci USA 2004; 101: 13306–11.
  • 54
    Nagahara H, Mimori K, Ohta M, Utsunomiya T, Inoue H, Barnard GF, Ohira M, Hirakawa K, Mori M. Somatic mutations of epidermal growth factor receptor in colorectal carcinoma. Clin Cancer Res 2005; 11: 1368–71.
  • 55
    Schilder RJ, Sill MW, Chen X, Darcy KM, Decesare SL, Lewandowski G, Lee RB, Arciero CA, Wu H, Godwin AK. Phase II study of gefitinib in patients with relapsed or persistent ovarian or primary peritoneal carcinoma and evaluation of epidermal growth factor receptor mutations and immunohistochemical expression: a Gynecologic Oncology Group Study. Clin Cancer Res 2005; 11: 5539–48.
  • 56
    Kwak EL, Jankowski J, Thayer SP, Lauwers GY, Brannigan BW, Harris PL, Okimoto RA, Haserlat SM, Driscoll DR, Ferry D, Muir B, Settleman J et al. Epidermal growth factor receptor kinase domain mutations in esophageal and pancreatic adenocarcinomas. Clin Cancer Res 2006; 12: 4283–7.
  • 57
    Prakash S, Sarran L, Socci N, DeMatteo RP, Eisenstat J, Greco AM, Maki RG, Wexler LH, LaQuaglia MP, Besmer P, Antonescu CR. Gastrointestinal stromal tumors in children and young adults: a clinicopathologic, molecular, and genomic study of 15 cases and review of the literature. J Pediatr Hematol Oncol 2005; 27: 179–87.
  • 58
    Price VE, Zielenska M, Chilton-MacNeill S, Smith CR, Pappo AS. Clinical and molecular characteristics of pediatric gastrointestinal stromal tumors (GISTs). Pediatr Blood Cancer 2005; 45: 20–4.
    Direct Link:
  • 59
    Matsui T, Sano K, Tsukamoto T, Ito M, Takaishi T, Nakata H, Nakamura H, Chihara K. Human neuroblastoma cells express α and β platelet-derived growth factor receptors coupling with neurotrophic and chemotactic signaling. J Clin Invest 1993; 92: 1153–60.
  • 60
    Cohen PS, Chan JP, Lipkunskaya M, Biedler JL, Seeger RC. Expression of stem cell factor and c-kit in human neuroblastoma. Blood. 1994; 84: 3465–72.
  • 61
    Uccini S, Mannarino O, McDowell HP, Pauser U, Vitali R, Natali PG, Altavista P, Andreano T, Coco S, Boldrini R, Bosco S, Clerico A et al. Clinical and molecular evidence for c-kit receptor as a therapeutic target in neuroblastic tumors. Clin Cancer Res 2005; 11: 380–9.
  • 62
    Meyers MB, Shen WP, Spengler BA, Ciccarone V, OBrien JP, Donner DB, Furth ME, Biedler JL. Increased epidermal growth factor receptor in multidrug-resistant human neuroblastoma cells. J Cell Biochem 1988; 38: 87–97.
    Direct Link:
  • 63
    Ho R, Minturn JE, Hishiki T, Zhao H, Wang Q, Cnaan A, Maris J, Evans AE, Brodeur GM. Proliferation of human neuroblastomas mediated by the epidermal growth factor receptor. Cancer Res 2005; 65: 9868–75.
  • 64
    Peng B, Hayes M, Resta D, Racine-Poon A, Druker BJ, Talpaz M, Sawyers CL, Rosamilia M, Ford J, Lloyd P, Capdeville R. Pharmacokinetics and pharmacodynamics of imatinib in a phase I trial with chronic myeloid leukemia patients. J Clin Oncol 2004; 22: 935–42.
  • 65
    Avramis IA, Laug WE, Sausville EA, Avramis VI. Determination of drug synergism between the tyrosine kinase inhibitors NSC 680410 (adaphostin) and/or STI571 (imatinib mesylate, Gleevec) with cytotoxic drugs against human leukemia cell lines. Cancer Chemother Pharmacol 2003; 52: 307–18.
  • 66
    Uehara H, Kim SJ, Karashima T, Shepherd DL, Fan D, Tsan R, Killion JJ, Logothetis C, Mathew P, Fidler IJ. Effects of blocking platelet-derived growth factor-receptor signaling in a mouse model of experimental prostate cancer bone metastases. J Natl Cancer Inst 2003; 95: 458–70.
  • 67
    Decaudin D, de Cremoux P, Sastre X, Judde JG, Nemati F, Tran-Perennou C, Freneaux P, Livartowski A, Pouillart P, Poupon MF. In vivo efficacy of STI571 in xenografted human small cell lung cancer alone or combined with chemotherapy. Int J Cancer 2005; 113: 849–56.
    Direct Link:
  • 68
    Kim R, Emi M, Arihiro K, Tanabe K, Uchida Y, Toge T. Chemosensitization by STI571 targeting the platelet-derived growth factor/platelet-derived growth factor receptor-signaling pathway in the tumor progression and angiogenesis of gastric carcinoma. Cancer 2005; 103: 1800–09.
    Direct Link:
  • 69
    Kubler HR, van Randenborgh H, Treiber U, Wutzler S, Battistel C, Lehmer A, Wagenpfeil S, Hartung R, Paul R. In vitro cytotoxic effects of imatinib in combination with anticancer drugs in human prostate cancer cell lines. Prostate 2005; 63: 385–94.
    Direct Link:
  • 70
    Wang-Rodriguez J, Lopez JP, Altuna X, Chu TS, Weisman RA, Ongkeko WM. STI-571 (Gleevec) potentiates the effect of cisplatin in inhibiting the proliferation of head and neck squamous cell carcinoma in vitro. Laryngoscope 2006; 116: 1409–16.
    Direct Link:
  • 71
    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: 229–39.
  • 72
    Houghton PJ, Cheshire PJ, Hallman JD,II, Lutz L, Friedman HS, Danks MK, Houghton JA. 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.
  • 73
    Chou TC, Motzer RJ, Tong Y, Bosl GJ. Computerised quantitation of synergism and antagonism of taxol, topotecan, and cisplatin against human teratocarcinoma cell growth: a rational approach to clinical protocol design. J Natl Cancer Inst 1994; 86: 1517–24.
  • 74
    Jonker JW, Smit JW, Brinkhuis RF, Maliepaard M, Beijnen JH, Schellens JH, Schinkel AH. Role of breast cancer resistance protein in the bioavailability and fetal penetration of topotecan. J Natl Cancer Inst 2000; 92: 1651–6.
  • 75
    Kruijtzer CM, Beijnen JH, Rosing H, ten Bokkel Huinink WW, Schot M, Jewell RC, Paul EM, Schellens JH. Increased oral bioavailability of topotecan in combination with the breast cancer resistance protein and P-glycoprotein inhibitor GF120918. J Clin Oncol 2002; 20: 2943–50.
  • 76
    Pietras K, Sjoblom T, Rubin K, Heldin CH, Ostman A. PDGF receptors as cancer drug targets. Cancer Cell 2003; 3: 439–43.
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