Disposition of 9-nitrocamptothecin and its 9-aminocamptothecin metabolite in relation to ABC transporter genotypes

Zamboni, William C.; Ramanathan, Ramesh K.; McLeod, Howard L.; Mani, Sridhar; Potter, Douglas M.; Strychor, Sandra; Maruca, Lauren; King, Cristi R.; Jung, Laura; Parise, Robert A.; Egorin, Merrill J.; Davis, Todd A.; Marsh, Sharon

doi:10.1007/s10637-006-6335-5

Cited by 42 publications

(23 citation statements)

References 30 publications

(66 reference statements)

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“…After intravenous administration, patients who were heterozygous for the 421A allele showed higher levels of plasma diflomotecan than those with wild-type sequences. Other studies reported that the heterozygous 421C>A was associated with increased oral bioavailability of topotecan and the lactone form of 9-aminocamptothecin [81,101]. These results suggest that carriers of the ABCG2 421C>A may have decreased clearance and/or increased oral bioavailability of ABCG2 substrate drugs.…”

Section: Abcg2 (Abcp Bcrp Mxr)mentioning

confidence: 71%

“…Innocenti et al identified 3972C>T as a SNP potentially affecting ABCC2 activity on irinotecan clearance, where the AUC of irinotecan and metabolites was higher in patients carrying two 3972T alleles [80]. However, a study on the disposition of 9-nitrocamptothecin and its metabolite in relation to ABCC2 polymorphism 3972C>T did not show a significant association [81]. Therefore, up to now the majority of genetic variants of ABCC2 which are not linked to DJS do not demonstrate a major importance for cancer therapy [82].…”

Section: Abcc2 (Cmoat Mrp2)mentioning

confidence: 99%

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Pharmacogenetics/genomics of membrane transporters in cancer chemotherapy

Huang

2007

Cancer Metastasis Rev

114

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Inter-individual variability in drug response and the emergence of adverse drug reactions are main causes of treatment failure in cancer therapy. Recently, membrane transporters have been recognized as an important determinant of drug disposition, thereby affecting chemosensitivity and -resistance. Genetic factors contribute to inter-individual variability in drug transport and targeting. Therefore, pharmacogenetic studies of membrane transporters can lead to new approaches for optimizing cancer therapy. This review discusses genetic variations in efflux transporters of the ATP-binding cassette (ABC) family such as ABCB1 (MDR1, P-glycoprotein), ABCC1 (MRP1), ABCC2 (MRP2) and ABCG2 (BCRP), and uptake transporters of the solute carrier (SLC) family such as SLC19A1 (RFC1) and SLCO1B1 (SLC21A6), and their relevance to cancer chemotherapy. Furthermore, a pharmacogenomic approach is outlined, which using correlations between the growth inhibitory potency of anticancer drugs and transporter gene expression in multiple human cancer cell lines, has shown promise for determining the relevant transporters for any given drugs and predicting anticancer drug response.

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Section: Abcg2 (Abcp Bcrp Mxr)mentioning

confidence: 71%

Section: Abcc2 (Cmoat Mrp2)mentioning

confidence: 99%

Pharmacogenetics/genomics of membrane transporters in cancer chemotherapy

Huang

2007

Cancer Metastasis Rev

114

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“…Expression of the Q141K SNP in cell lines has been shown to lead to significantly lower IC50 values for ABCG2 substrates, including mitoxantrone, irinotecan, and SN-38 [119,122]. The Q141K SNP has been shown to influence the pharmacokinetics of orally administered drugs, including topotecan [125], diflomotecan [126] and 9-aminocamptothecin [127]. As noted earlier, the higher plasma drug levels due to the Q141K SNP may result in exquisite sensitivity to certain orally administered chemotherapy drugs.…”

Section: Single Nucleotide Polymorphisms (Snps)mentioning

confidence: 99%

ABCG2: determining its relevance in clinical drug resistance

Robey

Polgár

Deeken

et al. 2007

Cancer Metastasis Rev

338

269

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Multidrug resistance is a major obstacle to successful cancer treatment. One mechanism by which cells can become resistant to chemotherapy is the expression of ABC transporters that use the energy of ATP hydrolysis to transport a wide variety of substrates across the cell membrane. There are three human ABC transporters primarily associated with the multidrug resistance phenomenon, namely Pgp, MRP1, and ABCG2. All three have broad and, to a certain extent, overlapping substrate specificities, transporting the major drugs currently used in cancer chemotherapy. ABCG2 is the most recently described of the three major multidrug-resistance pumps, and its substrates include mitoxantrone, topotecan, irinotecan, flavopiridol, and methotrexate. Despite several studies reporting ABCG2 expression in normal and malignant tissues, no trials have thus far addressed the role of ABCG2 in clinical drug resistance. This gives us an opportunity to critically review the disappointing results of past clinical trials targeting Pgp and to propose strategies for ABCG2. We need to know in which tumor types ABCG2 contributes to the resistance phenotype. We also need to develop standardized assays to detect ABCG2 expression in vivo and to carefully select the chemotherapeutic agents and clinical trial designs. This review focuses on our current knowledge about normal tissue distrubution, tumor expression profiles, and substrates and inhibitors of ABCG2, together with lessons learned from clinical trials with Pgp inhibitors. Implications of SNPs in the ABCG2 gene affecting the pharmacokinetics of substrate drugs, including many non-chemotherapy agents and ABCG2 expression in the SP population of stem cells are also discussed.

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“…However, de Jong et al reported that ABCG2 C421A genotype did not alter the disposition of irinotecan in European Caucasians [60] . In another study reported by Zamboni et al , ABCG2 genotype partly influenced the inter-individual variability of 9-aminocamptothecin when studied in relation to ABCG2 C421A genotype [61] . Gardner et al reported increased drug accumulation of imatinib, a tyrosine kinase enzyme inhibitor, in cell lines transfected with ABCG2 C421A [62] .…”

Section: Pharmacogenomics Of Abcg2/bcrpmentioning

confidence: 85%

“…Higher plasma levels Difl omotecan Patients Sparreboom 2004 [59] No change Irinotican Patients de Jong 2004 [60] Increased bioavailabilty 9-Aminocamptothecin Patients Zamboni 2006 [61] Increased accumulation Imatinib Transfected cell lines Gardner 2006 [62] Increased accumulation Topotecan Transfected cell lines Imai 2002 [142] No difference Imatinib Patients Gardner 2006 [62] Higher plasma levels Rosuvastatin Healthy volunteers Zhang 2006 [63] No change Pitavastatin Healthy volunteers Ieiri 2007 [64] Expert Opin. Drug Metab.…”

Section: C421a (Exon 5 Q141k)mentioning

confidence: 99%

Genetic variations and gene expression of transporters in drug disposition and response

Huang

Penchala²,

Pham³

et al. 2008

Expert Opinion on Drug Metabolism & Toxicology

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Background : The importance of transporters in drug disposition and response has led to increasing interest in genetic variations and expression differences of their genes. Objective : This review summarizes: i) genetic variations in transporters and associated drug response; and ii) a pharmacogenomic approach to correlate transporter expression and drug response. Methods : Several transporters in ATP-binding cassette family and solute carrier family are discussed. Conclusion : The field of transporter pharmacogenomics is in its early stage. Transporter expression at mRNA levels could be more directly related to their functions and more practical to be assayed in high throughput. Correlating microarray expression of transporters with anticancer drug activity in the NCI-60 panel has provided an approach for identifying drug-transporter relationships and predicting drug response.

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Disposition of 9-nitrocamptothecin and its 9-aminocamptothecin metabolite in relation to ABC transporter genotypes

Cited by 42 publications

References 30 publications

Pharmacogenetics/genomics of membrane transporters in cancer chemotherapy

Pharmacogenetics/genomics of membrane transporters in cancer chemotherapy

ABCG2: determining its relevance in clinical drug resistance

Genetic variations and gene expression of transporters in drug disposition and response

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