In acute lymphocytic leukemia (ALL), another hematopoietic malignancy, correlations between BCRP expression and drug response differed between studies21., 22.. precision medicine based on BCRP-mediated drug transport. expression or BCRP function. Understanding how these factors affect BCRP function is critical for the development of precision medicine approaches to accomplish optimized therapeutic effects and minimize adverse effects when prescribing specific drugs to patients. Open in a separate window 1.?Introduction Precision medicine is a rapidly-developing field in human healthcare that is influencing the practice of medicine. Based on each patient?s unique characteristics that affect responses to drugs, more accurate doses or drug treatments can be given to the patient to achieve better therapeutic benefits and less adverse reactions using a precision medicine approach. A patient?s individual characteristics that affect drug transporter action are an important aspect of precision medicine. Drug transporters are a class of proteins located on the membrane surface of cells that allow drugs to enter and exit cells carrier-mediated mechanisms1. Therapeutic efficacy and adverse reactions of drugs can be affected by the expression and function of drug transporters located in biological membrane barriers of a multitude of target tissues. Human breast cancer resistant protein (BCRP) is a key transporter involved in a patient?s idiosyncratic functionality with respect to drug transport. BCRP is so called because it was first recognized in breast malignancy cells that exhibited drug resistance to mitoxantrone, doxorubicin, and daunorubicin2. The human BCRP protein is usually encoded by the ATP-binding cassette subfamily G member 2 (gene, which is a member of the ATP-binding cassette transporter superfamily. Human BCRP is usually apically localized in the cell membranes of multiple organs3, including epithelial cells of the small intestine, the canalicular domain name of liver hepatocytes, renal tubule cells, brain capillary endothelial cells in blood-brain barrier, and placental syncytiotrophoblasts (Fig. 1)4., 5.. BCRP utilizes the energy generated from ATP hydrolysis to drive the efflux of diverse chemicals across cell membranes6, including both endogenous substrates, such as folic acid7 and uric acid8, and xenobiotics9, as well as environmental toxins, such as pheophorbide A10. Detailed information about BCRP substrates are discussed elsewhere11. Open in a separate window Physique 1 Tissue distribution of human BCRP. BCRP is usually highly expressed in several sites in human, including small intestine, liver, kidney, the bloodCbrain barrier, and placenta. The primary function of BCRP is usually to pump substrates from your intracellular space to the extracellular space. BCRP has been extensively analyzed for its role as an efflux transporter of drugs, leading to drug resistance in target cells and decreased pharmacological effects of substrate drugs. Overexpression of BCRP has been regarded as one of the causes of multi drug resistance (MDR) in diseases, especially cancer. In cell based studies, over expression of BCRP has been found to correlate with MDR in cells derived from several cancers, including breast cancer, ovarian malignancy, colon cancer, small cell lung malignancy, and myeloma2., 12., 13., 14., 15., 16.. In addition to cellular models, BCRP overexpression has been correlated with MDR and malignancy Memantine hydrochloride treatment outcomes in clinical settings. BCRP has also been found to be overexpressed in hematopoietic malignancies and solid tumors after chemotherapy treatment. In studies of acute myeloid leukemia (AML), high BCRP levels were reported in 33% of AML blast cells, which also correlated with disease prognosis and overall survival17., 18., 19.. However, no correlation between BCRP expression and overall AML incidence has been found20., 21.. In acute lymphocytic leukemia (ALL), another hematopoietic malignancy, correlations between BCRP expression and drug response differed between studies21., 22.. The roles of BCRP have also been assessed in multiple solid tumors with conflicting conclusions about overall survival Memantine hydrochloride or prognosis, Memantine hydrochloride including breast carcinoma, non-small cell lung cancer, melanoma, and retinoblastoma23., 24., 25., 26., 27.. The lack of consensus concerning the role of BCRP in these studies might stem from multiple sources, including BCRP detection methods, sample sizes, or patient composition. Despite the fact that the role of BCRP is still not completely understood, inhibition of BCRP has been considered as a pharmacological strategy to improve outcomes of drug Memantine hydrochloride treatment28., 29.. Differential expression and altered function of BCRP lead to dramatic inter-individual differences in drug response and disease progression. Several factors have been reported to be responsible for variations of BCRP expression and function. In this review, we summarize some well-documented factors, including genetic, epigenetic, physiologic, pathologic, and environmental factors in the regulation of BCRP expression and alterations of BCRP function. Combinations.Hesperetin, quercetin, daidzein, and stilbene resveratrol were also able to alter BCRP function for the transport of intracellular BCRP substrates105. of precision medicine based on BCRP-mediated drug transport. expression or BCRP function. Understanding how these factors affect BCRP function is critical for the development of precision medicine approaches to achieve optimized therapeutic effects and minimize adverse effects when prescribing specific drugs to patients. Open in a separate window 1.?Introduction Precision medicine is a rapidly-developing field in human healthcare that is influencing the practice of medicine. Based on each patient?s unique characteristics that affect responses to drugs, more accurate doses or drug treatments can be given to the patient to achieve better therapeutic benefits and less adverse reactions using a precision medicine approach. A patient?s individual characteristics that affect drug transporter action are an important aspect of precision medicine. Drug transporters are a class of proteins located on the membrane surface of cells that allow drugs to enter and exit cells carrier-mediated mechanisms1. Therapeutic efficacy and adverse reactions of drugs can be affected by the expression and function of drug transporters located in biological membrane barriers of a multitude of target tissues. Human breast cancer resistant protein (BCRP) is a key transporter involved in a patient?s idiosyncratic functionality with respect to drug transport. BCRP is so called because it was first identified in breast Rabbit Polyclonal to Estrogen Receptor-alpha (phospho-Tyr537) cancer cells that exhibited drug resistance to mitoxantrone, doxorubicin, and daunorubicin2. The human BCRP protein is encoded by the ATP-binding cassette subfamily G member 2 (gene, which is a member of the ATP-binding cassette transporter superfamily. Human BCRP is apically localized in the cell membranes of multiple organs3, including epithelial cells of the small intestine, the canalicular domain of liver hepatocytes, renal tubule cells, brain capillary endothelial cells in blood-brain barrier, and placental syncytiotrophoblasts (Fig. 1)4., 5.. BCRP utilizes the energy generated from ATP hydrolysis to drive the efflux of diverse chemicals across cell membranes6, including both endogenous substrates, such as folic acid7 and uric acid8, and xenobiotics9, as well as environmental toxins, such as pheophorbide A10. Detailed information about BCRP substrates are discussed elsewhere11. Open in a separate window Figure 1 Tissue distribution of human BCRP. BCRP is highly expressed in several sites in human, including small intestine, liver, kidney, the bloodCbrain barrier, and placenta. The primary function of BCRP is to pump substrates from the intracellular space to the extracellular space. BCRP has been extensively studied for its role as an efflux transporter of drugs, leading to drug resistance in target cells and decreased pharmacological effects of substrate drugs. Overexpression of BCRP has been regarded as one of the causes of multi drug resistance (MDR) in diseases, especially cancer. In cell based studies, over expression of BCRP Memantine hydrochloride has been found to correlate with MDR in cells derived from several cancers, including breast cancer, ovarian cancer, colon cancer, small cell lung cancer, and myeloma2., 12., 13., 14., 15., 16.. In addition to cellular models, BCRP overexpression has been correlated with MDR and cancer treatment outcomes in clinical settings. BCRP has also been found to be overexpressed in hematopoietic malignancies and solid tumors after chemotherapy treatment. In studies of acute myeloid leukemia (AML), high BCRP levels were reported in 33% of AML blast cells, which also correlated with disease prognosis and overall survival17., 18., 19.. However, no correlation between BCRP expression and overall AML incidence has been found20., 21.. In acute lymphocytic leukemia (ALL), another hematopoietic malignancy, correlations between BCRP expression and drug response differed between studies21., 22.. The roles of BCRP have also been assessed in multiple solid tumors with conflicting conclusions about overall survival or prognosis, including breast carcinoma, non-small cell lung cancer, melanoma, and retinoblastoma23., 24., 25., 26., 27.. The lack of consensus concerning the role of BCRP in these studies might stem from multiple sources, including BCRP detection methods, sample sizes, or patient composition. Despite the fact that the role of BCRP is still not completely.
In acute lymphocytic leukemia (ALL), another hematopoietic malignancy, correlations between BCRP expression and drug response differed between studies21
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