A Mutation in the Promoter of the Multidrug Resistance Gene (MDR1) in Human Hematological Malignancies may Contribute to the Pathogenesis of Resistant Disease

Rund, Deborah; Azar, Idit; Shperling, Olga

doi:10.1007/978-1-4615-4811-9_9

Cited by 33 publications

(18 citation statements)

References 16 publications

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“…After treatment with ABCB1 substrate drugs, the +103T>C lead to increased transcritional activity in an in vitro reporter assay compared with the wildtype controls [19,20]. Another SNP (+8T>C) was found in the ABCB1 promoter from hematological malignancies, but the effect on gene function was unknown because it was similarly detected in normal controls [21]. 2677G>T in exon 21 and 2995G>A/T in exon 24 were reported by Mickley et al [22], leading to amino acid changes of A893S and A999T, respectively.…”

Section: Abcb1 (Mdr1 P-glycoprotein)mentioning

confidence: 93%

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: Abcb1 (Mdr1 P-glycoprotein)mentioning

confidence: 93%

Pharmacogenetics/genomics of membrane transporters in cancer chemotherapy

Huang

2007

Cancer Metastasis Rev

114

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“…In a study evaluating MDR1 promoter mutations in human tumors, 15 of 39 patients were found to have a point mutation (T-C transition) at þ 8 relative to the start site of transcription (Rund et al, 1999). In a second study evaluating the role of MDR1 mutations and polymorphisms in colo-rectal cancer, naturally occurring mutations in the promoter region were associated with colon cancers exhibiting high microsatellite instability (Potocnik et al, 2002).…”

Section: Gene Rearrangements and Mutationsmentioning

confidence: 99%

Transcriptional regulation of ABC drug transporters

2003

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“…To date, many single-nucleotide polymorphisms (SNP) of the ABCB1 gene have been identified (Hoffmeyer et al, 2000). Depending on the type of SNP, MDR1 genetic variants can impact target cell concentrations of P-gp/MDR1 substrates, either increasing or decreasing therapy resistance (Rund et al, 1999). The C3435T polymorphism, which was found significantly in correlation with the function of MDR1 and the expression of P-gp, also affects the clinical drug response and results of the treatment (Illmer et al, 2002;Marzolini et al, 2004;Babaoglu et al, 2005).…”

Section: Introductionmentioning

confidence: 99%