Transport of Topoisomerase I Inhibitors by the Breast Cancer Resistance Protein: Potential Clinical Implications

Schellens, Jan H.M.; Maliepaard, Marc; Scheper, Rik J.; Scheffer, George L.; Jonker, Johan W.; Smit, Johan W.; Beijnen, Jos H.; Schinkel, Alfred H.

doi:10.1111/j.1749-6632.2000.tb07037.x

Cited by 108 publications

(54 citation statements)

References 18 publications

(31 reference statements)

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“…Furthermore, although the lactone form can freely enter cells via passive diffusion across cell membranes, their intracellular concentration is greatly reduced by efflux pumps in a wide variety of tissues (5, 39 -43). Multidrug resistance (MDR) results from drug efflux by the well-characterized P-glycoprotein for which both topotecan and irinotecan are substrates (40). Additionally, camptothecins are substrates for the pump known as breast cancer-resistant protein (BCRP; refs.…”

Section: Introductionmentioning

confidence: 99%

Bone marrow and tumor cell colony-forming units and human tumor xenograft efficacy of noncamptothecin and camptothecin topoisomerase I inhibitors

Kurtzberg¹,

Battle²,

Rouleau³

et al. 2008

Molecular Cancer Therapeutics

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Topoisomerase I (TopoI), an established anticancer target, is an enzyme producing a single-strand DNA break during transcription. Several noncamptothecin TopoI inhibitors have been identified. One of these, ARC-111, was compared with two clinically used camptothecins, topotecan and irinotecan/SN-38. In mouse and human bone marrow colony formation [colony-forming units granulocytemacrophage (CFU-GM)] assays, the IC 90 values were 519 and 331 nmol/L for topotecan and SN-38 mouse CFU-GM and were 19 and 26 nmol/L for human CFU-GM, giving mouse to human differentials of 28-and 13-fold. ARC-111 produced IC 90 values of 28 nmol/L in mouse and 6.2 nmol/L in human CFU-GM, thus only a 4.5-fold differential between species. Human bone marrow CFU-GM was more sensitive to topotecan than were several human cancer cell lines, but ARC-111 cytotoxicity was similar for human bone marrow CFU-GM and the seven human tumor cell lines tested. In HCT-116 xenografts, tumor growth delays (TGD) were 17 days for irinotecan and 20 days for ARC-111. In HT-29 xenografts, the TGD was 9 days for both irinotecan and ARC-111. Both ARC-111 and docetaxel had a TGD of 21 days in NCI-H460

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Section: Introductionmentioning

confidence: 99%

Bone marrow and tumor cell colony-forming units and human tumor xenograft efficacy of noncamptothecin and camptothecin topoisomerase I inhibitors

Kurtzberg¹,

Battle²,

Rouleau³

et al. 2008

Molecular Cancer Therapeutics

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“…On the other hand, overexpression of ABC proteins such as ABCB1 and ABCC1 seems to trigger multidrug resistance, a major obstacle in cancer chemotherapy. Another member of the ABC family of drug transporters, the breast cancer resistance protein ABCG2, also mediates resistance to camptothecins (18).…”

Section: Introductionmentioning

confidence: 99%

Gene Expression Profiling of the Irinotecan Pathway in Colorectal Cancer

Shannon

Watson³

et al. 2005

Clinical Cancer Research

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The exact mechanism responsible for large variation of response to chemotherapy remains unclear. This study profiled the gene expression for the entire irinotecan pathway to provide insights into individualized cancer therapy. The RNA expressions of 24 irinotecan pathway genes were measured in paired tumor and normal tissues from 52 patients with Dukes' C colorectal cancer using a real-time quantitative reverse transcription-PCR assay. The relative expression levels across the 24 pathway genes varied considerably, with a 441-fold range from highest to lowest expression levels for the tumor tissues and a 934-fold range for the normal tissues. Interpatient variability was also quite large, with a 33.6 median fold change in the tumor tissue genes and a 30.1 median fold change in the normal tissue genes. Six of the 24 irinotecan pathway genes had dramatically lower expression levels in the tumor samples than did the genes in the normal tissues (median range, 1.28-4.39 folds; P = 0.001-0.029). Eight genes had significantly higher levels (median range, 1.35-2.42 folds; P = 0.001-0.011). Using hierarchical clustering, three gene clusters and three patient groups were observed with high similarity indices by the RNA expressions in colorectal tumors. The three patient groups had no unique clinical pathologic features but could be differentiated by the statistically significant differences in RNA expression level of seven genes. Our study indicates that gene expression profiling could be valuable for predicting tumor response to chemotherapy and for tailoring therapy to individual cancer patients.

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“…Based on a series of cellular, animal and human studies, we now realize that both intestinal metabolic enzymes and efflux transporters, working together as a protective mechanism, may be responsible for the poor bioavailability of a number of drugs (Furuta T, 1998;Schellens JH, 2000;Luo FR, 2002). Drug metabolizing enzymes and drug-transporters critically regulate the extent of drug distribution throughout the body and the rate of drug clearance from the body (Volm M, 1991;Wacher VJ, 1995).…”

Section: Drug Metabolizing Enzymes and Drug-transportersmentioning

confidence: 99%

Pharmacogenomics Dictate Pharmacokinetics: Polymorphisms in Drug-Metabolizing Enzymes and Drug-Transporters

Mondal¹,

Gerlach²,

Datta³

et al. 2012

Readings in Advanced Pharmacokinetics - Theory, Methods and Applications

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Transport of Topoisomerase I Inhibitors by the Breast Cancer Resistance Protein: Potential Clinical Implications

Cited by 108 publications

References 18 publications

Bone marrow and tumor cell colony-forming units and human tumor xenograft efficacy of noncamptothecin and camptothecin topoisomerase I inhibitors

Bone marrow and tumor cell colony-forming units and human tumor xenograft efficacy of noncamptothecin and camptothecin topoisomerase I inhibitors

Gene Expression Profiling of the Irinotecan Pathway in Colorectal Cancer

Pharmacogenomics Dictate Pharmacokinetics: Polymorphisms in Drug-Metabolizing Enzymes and Drug-Transporters

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