Do SLCO1B3 (T334G) and CYP3A5*3 polymorphisms affect response in Egyptian chronic myeloid leukemia patients receiving imatinib therapy?

Bedewy, Ahmed M.; EL-Maghraby, Shereen M.

doi:10.1179/1607845412y.0000000067

Cited by 21 publications

(20 citation statements)

References 22 publications

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“…However, some of the studies have identified the involvement of single nucleotide polymorphism (SNPs) in inter‐individual and inter‐population pharmacokinetic variability The data reported are not sufficiently conclusive to translate into individual drug‐dosage adjustment. It is noteworthy that only one of these studies was conducted in African patients and none was from Nigeria where the drug has also been introduced as the drug of first choice for CML. Therefore, in the present study we investigated the association of genetic polymorphism in the genes encoding for CYP3A5 , ABCG2 and ABCB1 with the steady‐state trough plasma concentrations and clinical outcomes of imatinib in Nigerians with CML.…”

Section: What Is Known and Objectivementioning

confidence: 99%

Influence of CYP3A5*3 and ABCB1 C3435T on clinical outcomes and trough plasma concentrations of imatinib in Nigerians with chronic myeloid leukaemia

et al. 2016

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Section: What Is Known and Objectivementioning

confidence: 99%

Influence of CYP3A5*3 and ABCB1 C3435T on clinical outcomes and trough plasma concentrations of imatinib in Nigerians with chronic myeloid leukaemia

et al. 2016

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“…In vitro mTORC2 kinase assays and immunoprecipitations were performed using anti-Rictor antibody. E, SMMC-7721 cell lines were serum-starved overnight and pretreated with or without H2O2 (100 mmol/L) for 30 minutes before HGF ( cancerres.aacrjournals.org Downloaded from major aspects, the potential relationship of CYP3A5 polymorphism and cancer risk or drug metabolism (9)(10)(11)(21)(22)(23)(24)(25)(26). Moreover, Tsunedomi R concluded that the expression of CYP3A5 was drastically decreased in conjunction with venous invasion and might serve as a marker of progression and molecular target for treatment of HCV-associated HCC (27).…”

Section: Cyp3a5-induced Intracellular Ros Enrichment Is Responsible Fmentioning

confidence: 99%

CYP3A5 Functions as a Tumor Suppressor in Hepatocellular Carcinoma by Regulating mTORC2/Akt Signaling

et al. 2015

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CYP3A5 is a cytochrome P450 protein that functions in the liver metabolism of many carcinogens and cancer drugs. However, it has not been thought to directly affect cancer progression. In this study, we challenge this perspective by demonstrating that CYP3A5 is downregulated in many hepatocellular carcinomas (HCC), where it has an important role as a tumor suppressor that antagonizes the malignant phenotype. CYP3A5 was downregulated in multiple cohorts of human HCC examined. Lower CYP3A5 levels were associated with more aggressive vascular invasion, poor differentiation, shorter time to disease recurrence after treatment, and worse overall patient survival. Mechanistic investigations showed that CYP3A5 overexpression limited MMP2/9 function and suppressed HCC migration and invasion in vitro and in vivo by inhibiting AKT signaling. Notably, AKT phosphorylation at Ser473 was inhibited in CYP3A5-overexpressing HCC cells, an event requiring mTORC2 but not Rictor/mTOR complex formation. CYP3A5-induced ROS accumulation was found to be a critical upstream regulator of mTORC2 activity, consistent with evidence of reduced GSH redox activity in most clinical HCC specimens with reduced metastatic capacity. Taken together, our results defined CYP3A5 as a suppressor of HCC pathogenesis and metastasis with potential utility a prognostic biomarker. Cancer Res; 75(7); 1470-81. Ó2015 AACR.

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“…Preliminary evidence supporting this thesis comes from a study in which genetic variation in OATP1B3 was shown to be linked with altered concentrations of imatinib in circulating cells as well as with altered oral clearance of the drug (Nambu et al, 2011). However, this same variant was not associated with response to treatment (Bedewy and El-Maghraby, 2013), and there is no evidence that this transporter is connected with imatinib-induced adverse events that would be either directly associated with uptake in a target tissue or indirectly through an effect on systemic drug levels.…”

Section: Tyrosine Kinase Inhibitorsmentioning

confidence: 89%

Uptake Carriers and Oncology Drug Safety

Sprowl

Sparreboom

2013

Drug Metab Dispos

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Members of the solute carrier (SLC) family of transporters are responsible for the cellular influx of a broad range of endogenous compounds and xenobiotics in multiple tissues. Many of these transporters are highly expressed in the gastrointestinal tract, liver, and kidney and are considered to be of particular importance in governing drug absorption, elimination, and cellular sensitivity of specific organs to a wide variety of oncology drugs. Although the majority of studies on the interaction of oncology drugs with SLC have been restricted to the use of exploratory in vitro model systems, emerging evidence suggests that several SLCs, including OCT2 and OATP1B1, contribute to clinically important phenotypes associated with those agents. Recent literature has indicated that modulation of SLC activity may result in drug-drug interactions, and genetic polymorphisms in SLC genes have been described that can affect the handling of substrates. Alteration of SLC function by either of these mechanisms has been demonstrated to contribute to interindividual variability in the pharmacokinetics and toxicity associated with several oncology drugs. In this report, we provide an update on this rapidly emerging field.

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Do SLCO1B3 (T334G) and CYP3A5*3 polymorphisms affect response in Egyptian chronic myeloid leukemia patients receiving imatinib therapy?

Cited by 21 publications

References 22 publications

Influence of CYP3A5*3 and ABCB1 C3435T on clinical outcomes and trough plasma concentrations of imatinib in Nigerians with chronic myeloid leukaemia

Influence of CYP3A5*3 and ABCB1 C3435T on clinical outcomes and trough plasma concentrations of imatinib in Nigerians with chronic myeloid leukaemia

CYP3A5 Functions as a Tumor Suppressor in Hepatocellular Carcinoma by Regulating mTORC2/Akt Signaling

Uptake Carriers and Oncology Drug Safety

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