Cancer Research Annual Meeting 2010 Jordan
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Erlichman, C.
Right arrow Articles by Kaufmann, S. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Erlichman, C.
Right arrow Articles by Kaufmann, S. H.
[Cancer Research 61, 739-748, January 15, 2001]
© 2001 American Association for Cancer Research

Experimental Therapeutics

The HER Tyrosine Kinase Inhibitor CI1033 Enhances Cytotoxicity of 7-Ethyl-10-hydroxycamptothecin and Topotecan by Inhibiting Breast Cancer Resistance Protein-mediated Drug Efflux1

Charles Erlichman2, Scott A. Boerner, Christopher G. Hallgren, Rebecca Spieker, Xiao-Yang Wang, C. David James, George L. Scheffer, Marc Maliepaard, Douglas D. Ross, Keith C. Bible and Scott H. Kaufmann2

Divisions of Medical Oncology [C. E., K. C. B.] and Oncology Research [S. A. B., C. G. H., R. S., S. H. K.] and Department of Laboratory Medicine [X-Y. W., C. D. J.], Mayo Clinic and Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Graduate School [K. C. B., S. H. K.], Rochester, Minnesota 55905; University of Maryland Greenebaum Cancer Center and Baltimore Veterans Medical Center, Baltimore, Maryland 21201 [D. D. R.]; Department of Pathology, Free University Hospital, 1081 HV Amsterdam, the Netherlands [G. L. S.]; and Division of Experimental Therapy, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands [M. M.]

Because the activities of HER family members are elevated and/or aberrant in a variety of human neoplasms, these cell surface receptors are receiving increasing attention as potential therapeutic targets. In the present study, we examined the effect of combining the HER family tyrosine kinase inhibitor CI1033 (PD 183805) with the topoisomerase (topo) I poison 7-ethyl-10-hydroxycamptothecin (SN-38), the active metabolite of irinotecan, in a number of different cell lines. Colony-forming assays revealed that the antiproliferative effects of simultaneous treatment with CI1033 and SN-38 were synergistic in T98G glioblastoma cells and HCT8 colorectal carcinoma cells, whereas sequential treatments were additive at best. In additional studies examining the mechanistic basis for these findings in T98G cells, immunoblotting revealed that the inhibitory effects of CI1033 on epidermal growth factor receptor autophosphorylation were unaffected by SN-38. Likewise, CI1033 had no effect on topo I polypeptide levels, localization, or activity. Nonetheless, CI1033 markedly enhanced the number of covalent topo I-DNA complexes stabilized by SN-38 or the related agent topotecan (TPT). Analysis of intracellular SN-38 levels by high-performance liquid chromatography and intracellular TPT levels by flow microfluorometry revealed that CI1033 increased the steady-state accumulation of SN-38 and TPT by 9.4 ± 1.9- and 1.8 ± 0.2-fold, respectively. Further evaluation revealed that the initial rate of TPT uptake was unaffected by CI1033, whereas the rate of efflux was markedly diminished. Additional studies demonstrated that T98G and HCT8 cells express the breast cancer resistance protein (BCRP), a recently cloned ATP binding cassette transporter. Moreover, CI1033 enhanced the uptake and cytotoxicity of SN-38 and TPT in cells transfected with BCRP but not empty vector. Conversely, CI1033 accumulation was diminished in cells expressing BCRP, suggesting that CI1033 is a substrate for this efflux pump. These results indicate that CI1033 can modulate the accumulation and subsequent cytotoxicity of two widely used topo I poisons in cells that have no history of previous exposure to these agents.




This article has been cited by other articles:


Home page
 Drug Metab. Dispos.Home page
S. Shukla, R. W. Robey, S. E. Bates, and S. V. Ambudkar
Sunitinib (Sutent, SU11248), a Small-Molecule Receptor Tyrosine Kinase Inhibitor, Blocks Function of the ATP-Binding Cassette (ABC) Transporters P-Glycoprotein (ABCB1) and ABCG2
Drug Metab. Dispos., February 1, 2009; 37(2): 359 - 365.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
J. R. Molina, S. H. Kaufmann, J. M. Reid, S. D. Rubin, M. Galvez-Peralta, R. Friedman, K. S. Flatten, K. M. Koch, T. M. Gilmer, R. J. Mullin, et al.
Evaluation of Lapatinib and Topotecan Combination Therapy: Tissue Culture, Murine Xenograft, and Phase I Clinical Trial Data
Clin. Cancer Res., December 1, 2008; 14(23): 7900 - 7908.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
C.-l. Dai, A. K. Tiwari, C.-P. Wu, X.-d. Su, S.-R. Wang, D.-g. Liu, C. R. Ashby Jr., Y. Huang, R. W. Robey, Y.-j. Liang, et al.
Lapatinib (Tykerb, GW572016) Reverses Multidrug Resistance in Cancer Cells by Inhibiting the Activity of ATP-Binding Cassette Subfamily B Member 1 and G Member 2
Cancer Res., October 1, 2008; 68(19): 7905 - 7914.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
A. K. McCollum, C. J. TenEyck, B. Stensgard, B. W. Morlan, K. V. Ballman, R. B. Jenkins, D. O. Toft, and C. Erlichman
P-Glycoprotein-Mediated Resistance to Hsp90-Directed Therapy Is Eclipsed by the Heat Shock Response
Cancer Res., September 15, 2008; 68(18): 7419 - 7427.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
P. Haluska, J. M. Carboni, C. TenEyck, R. M. Attar, X. Hou, C. Yu, M. Sagar, T. W. Wong, M. M. Gottardis, and C. Erlichman
HER receptor signaling confers resistance to the insulin-like growth factor-I receptor inhibitor, BMS-536924
Mol. Cancer Ther., September 1, 2008; 7(9): 2589 - 2598.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
Z. Shi, X.-X. Peng, I.-W. Kim, S. Shukla, Q.-S. Si, R. W. Robey, S. E. Bates, T. Shen, C. R. Ashby Jr., L.-W. Fu, et al.
Erlotinib (Tarceva, OSI-774) Antagonizes ATP-Binding Cassette Subfamily B Member 1 and ATP-Binding Cassette Subfamily G Member 2 Mediated Drug Resistance
Cancer Res., November 15, 2007; 67(22): 11012 - 11020.
[Abstract] [Full Text] [PDF]

Home page
 The OncologistHome page
M. O'Brien, J. Eckardt, and R. Ramlau
Recent Advances with Topotecan in the Treatment of Lung Cancer
Oncologist, October 1, 2007; 12(10): 1194 - 1204.
[Abstract] [Full Text] [PDF]

Home page
 The OncologistHome page
L. V. Sequist
Second-Generation Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Non-Small Cell Lung Cancer
Oncologist, March 1, 2007; 12(3): 325 - 330.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
Y. Zhuang, C. H. Fraga, K. E. Hubbard, N. Hagedorn, J. C. Panetta, C. M. Waters, and C. F. Stewart
Topotecan Central Nervous System Penetration Is Altered by a Tyrosine Kinase Inhibitor
Cancer Res., December 1, 2006; 66(23): 11305 - 11313.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
L. L. Garland, M. Hidalgo, D. S. Mendelson, D. P. Ryan, B. K. Arun, J. L. Lovalvo, I. A. Eiseman, S. C. Olson, P. F. Lenehan, and J. P. Eder
A Phase I Clinical and Pharmacokinetic Study of Oral CI-1033 in Combination with Docetaxel in Patients with Advanced Solid Tumors.
Clin. Cancer Res., July 15, 2006; 12(14): 4274 - 4282.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
M. Leggas, J. C. Panetta, Y. Zhuang, J. D. Schuetz, B. Johnston, F. Bai, B. Sorrentino, S. Zhou, P. J. Houghton, and C. F. Stewart
Gefitinib Modulates the Function of Multiple ATP-Binding Cassette Transporters In vivo.
Cancer Res., May 1, 2006; 66(9): 4802 - 4807.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
G. Yang, D. C. Pevear, M. H. Davies, M. S. Collett, T. Bailey, S. Rippen, L. Barone, C. Burns, G. Rhodes, S. Tohan, et al.
An Orally Bioavailable Antipoxvirus Compound (ST-246) Inhibits Extracellular Virus Formation and Protects Mice from Lethal Orthopoxvirus Challenge
J. Virol., October 15, 2005; 79(20): 13139 - 13149.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
N. C. Daw, W. L. Furman, C. F. Stewart, L. C. Iacono, M. Krailo, M. L. Bernstein, J. E. Dancey, R. A. Speights, S. M. Blaney, J. M. Croop, et al.
Phase I and Pharmacokinetic Study of Gefitinib in Children With Refractory Solid Tumors: A Children's Oncology Group Study
J. Clin. Oncol., September 1, 2005; 23(25): 6172 - 6180.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
X.-f. Zhou, X. Yang, Q. Wang, R. A. Coburn, and M. E. Morris
EFFECTS OF DIHYDROPYRIDINES AND PYRIDINES ON MULTIDRUG RESISTANCE MEDIATED BY BREAST CANCER RESISTANCE PROTEIN: IN VITRO AND IN VIVO STUDIES
Drug Metab. Dispos., August 1, 2005; 33(8): 1220 - 1228.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
T. Takada, H. Suzuki, Y. Gotoh, and Y. Sugiyama
REGULATION OF THE CELL SURFACE EXPRESSION OF HUMAN BCRP/ABCG2 BY THE PHOSPHORYLATION STATE OF AKT IN POLARIZED CELLS
Drug Metab. Dispos., July 1, 2005; 33(7): 905 - 909.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
J. Nemunaitis, I. Eiseman, C. Cunningham, N. Senzer, A. Williams, P. F. Lenehan, S. C. Olson, P. Bycott, M. Schlicht, R. Zentgraff, et al.
Phase 1 Clinical and Pharmacokinetics Evaluation of Oral CI-1033 in Patients with Refractory Cancer
Clin. Cancer Res., May 15, 2005; 11(10): 3846 - 3853.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
Y. Nakamura, M. Oka, H. Soda, K. Shiozawa, M. Yoshikawa, A. Itoh, Y. Ikegami, J. Tsurutani, K. Nakatomi, T. Kitazaki, et al.
Gefitinib ("Iressa", ZD1839), an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor, Reverses Breast Cancer Resistance Protein/ABCG2-Mediated Drug Resistance
Cancer Res., February 15, 2005; 65(4): 1541 - 1546.
[Abstract] [Full Text] [PDF]

Home page
 Ann OncolHome page
J. P. Spano, R. Fagard, J.-C. Soria, O. Rixe, D. Khayat, and G. Milano
Epidermal growth factor receptor signaling in colorectal cancer: preclinical data and therapeutic perspectives
Ann. Onc., February 1, 2005; 16(2): 189 - 194.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
P.L. R. Ee, X. He, D. D. Ross, and W. T. Beck
Modulation of breast cancer resistance protein (BCRP/ABCG2) gene expression using RNA interference
Mol. Cancer Ther., December 1, 2004; 3(12): 1577 - 1584.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
C. F. Stewart, M. Leggas, J. D. Schuetz, J. C. Panetta, P. J. Cheshire, J. Peterson, N. Daw, J. J. Jenkins III, R. Gilbertson, G. S. Germain, et al.
Gefitinib Enhances the Antitumor Activity and Oral Bioavailability of Irinotecan in Mice
Cancer Res., October 15, 2004; 64(20): 7491 - 7499.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
F. Munoz-Martinez, P. Lu, F. Cortes-Selva, J. M. Perez-Victoria, I. A. Jimenez, A. G. Ravelo, F. J. Sharom, F. Gamarro, and S. Castanys
Celastraceae Sesquiterpenes as a New Class of Modulators That Bind Specifically to Human P-Glycoprotein and Reverse Cellular Multidrug Resistance
Cancer Res., October 1, 2004; 64(19): 7130 - 7138.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
K. Yanase, S. Tsukahara, S. Asada, E. Ishikawa, Y. Imai, and Y. Sugimoto
Gefitinib reverses breast cancer resistance protein-mediated drug resistance
Mol. Cancer Ther., September 1, 2004; 3(9): 1119 - 1125.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
C. Ozvegy-Laczka, T. Heged""s, G. Varady, O. Ujhelly, J. D. Schuetz, A. Varadi, G. Keri, L. Orfi, K. Nemet, and B. Sarkadi
High-Affinity Interaction of Tyrosine Kinase Inhibitors with the ABCG2 Multidrug Transporter
Mol. Pharmacol., June 1, 2004; 65(6): 1485 - 1495.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
P. J. Houghton, G. S. Germain, F. C. Harwood, J. D. Schuetz, C. F. Stewart, E. Buchdunger, and P. Traxler
Imatinib Mesylate Is a Potent Inhibitor of the ABCG2 (BCRP) Transporter and Reverses Resistance to Topotecan and SN-38 in Vitro
Cancer Res., April 1, 2004; 64(7): 2333 - 2337.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
N. C. Daw, V. M. Santana, L. C. Iacono, W. L. Furman, D. R. Hawkins, P. J. Houghton, J. C. Panetta, A. J. Gajjar, and C. F. Stewart
Phase I and Pharmacokinetic Study of Topotecan Administered Orally Once Daily for 5 Days for 2 Consecutive Weeks to Pediatric Patients With Refractory Solid Tumors
J. Clin. Oncol., March 1, 2004; 22(5): 829 - 837.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
M. K. Nyati, D. Maheshwari, S. Hanasoge, A. Sreekumar, S. D. Rynkiewicz, A. M. Chinnaiyan, W. R. Leopold, S. P. Ethier, and T. S. Lawrence
Radiosensitization by Pan ErbB Inhibitor CI-1033 in Vitro and in Vivo
Clin. Cancer Res., January 15, 2004; 10(2): 691 - 700.
[Abstract] [Full Text] [PDF]

Home page
 The OncologistHome page
M. L. Janmaat and G. Giaccone
Small-Molecule Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors
Oncologist, December 1, 2003; 8(6): 576 - 586.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
R. Rajendra, M. K. Gounder, A. Saleem, J. H. M. Schellens, D. D. Ross, S. E. Bates, P. Sinko, and E. H. Rubin
Differential Effects of the Breast Cancer Resistance Protein on the Cellular Accumulation and Cytotoxicity of 9-Aminocamptothecin and 9-Nitrocamptothecin
Cancer Res., June 15, 2003; 63(12): 3228 - 3233.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
J. D. Allen, S. C. van Dort, M. Buitelaar, O. van Tellingen, and A. H. Schinkel
Mouse Breast Cancer Resistance Protein (Bcrp1/Abcg2) Mediates Etoposide Resistance and Transport, but Etoposide Oral Availability Is Limited Primarily by P-glycoprotein
Cancer Res., March 15, 2003; 63(6): 1339 - 1344.
[Abstract] [Full Text] [PDF]

Home page
 Br Med BullHome page
J. S de Bono and E. K Rowinsky
Therapeutics targeting signal transduction for patients with colorectal carcinoma
Br. Med. Bull., December 1, 2002; 64(1): 227 - 254.
[Abstract] [Full Text] [PDF]

Home page
 The OncologistHome page
C.M.F. Kruijtzer, J.H. Beijnen, and J.H.M. Schellens
Improvement of Oral Drug Treatment by Temporary Inhibition of Drug Transporters and/or Cytochrome P450 in the Gastrointestinal Tract and Liver: An Overview
Oncologist, December 1, 2002; 7(6): 516 - 530.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
D. F.S. Kehrer, R. H.J. Mathijssen, J. Verweij, P. de Bruijn, and A. Sparreboom
Modulation of Irinotecan Metabolism by Ketoconazole
J. Clin. Oncol., July 15, 2002; 20(14): 3122 - 3129.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
G. K. Dy and A. A. Adjei
Novel Targets for Lung Cancer Therapy: Part I
J. Clin. Oncol., June 15, 2002; 20(12): 2881 - 2894.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
J. D. Allen and A. H. Schinkel
Multidrug Resistance and Pharmacological Protection Mediated by the Breast Cancer Resistance Protein (BCRP/ABCG2)
Mol. Cancer Ther., April 1, 2002; 1(6): 427 - 434.
[Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2001 by the American Association for Cancer Research.