Precision medicine is a rapidly-developing modality of medicine in human healthcare.Based on each patient’s unique characteristics, more accurate dosages and drug selection can be made to achieve better therapeutic e...Precision medicine is a rapidly-developing modality of medicine in human healthcare.Based on each patient’s unique characteristics, more accurate dosages and drug selection can be made to achieve better therapeutic efficacy and less adverse reactions in precision medicine. A patient’s individual parameters that affect drug transporter action can be used to develop a precision medicine guidance, due to the fact that therapeutic efficacy and adverse reactions of drugs can both be affected by expression and function of drug transporters on the cell membrane surface. The purpose of this review is to summarize unique characteristics of human breast cancer resistant protein(BCRP) and the genetic variability in the BCRP encoded gene ABCG2 in the development of precision medicine. Inter-individual variability of BCRP/ABCG2 can impact choices and outcomes of drug treatment for several diseases, including cancer chemotherapy. Several factors have been implicated in expression and function of BCRP, including genetic, epigenetic, physiologic,pathologic, and environmental factors. Understanding the roles of these factors in controlling expression and function of BCRP is critical for the development of precision medicine based on BCRP-mediated drug transport.展开更多
The host-dependent nature of idiosyncratic drug-induced liver injury(iDILI)suggests that rare genetic polymorphisms may contribute to the disease.Indeed,a few mutations in key genes have already been identified using ...The host-dependent nature of idiosyncratic drug-induced liver injury(iDILI)suggests that rare genetic polymorphisms may contribute to the disease.Indeed,a few mutations in key genes have already been identified using conventional human genetics approaches.Over 50 commonly used drugs can precipitate iDILI,making this a substantial medical problem.Only recently have human induced pluripotent stem cells been used as a research tool to discover novel iDILI genes and to study the mechanisms of iDILI in vitro.Here we review the current state of stem cell use in the investigation of iDILI,with a special focus on genetics.In addition,the concerns and difficulties associated with genetics and animal model research are discussed.We then present the features of patient-specific pluripotent stem cells(which may be derived from iDILI patients themselves),and explain why these cells may be of great utility.A variety of recent approaches to produce hepatocyte-like cells from pluripotent cells and the associated advantages and limitations of such cells are discussed.Future directions for the use of stem cell science to investigate iDILI include novel ways to identify new iDILI genes,a consideration of epigenetic impacts on iDILI,and the development of new and improved strategies for the production of hepatocytes from human pluripotent cells.展开更多
基金supported in the part by National Institutes of Health National Institute of General Medical Sciences,USA(R01GM118367 to Xiao-bo Zhong,USA)
文摘Precision medicine is a rapidly-developing modality of medicine in human healthcare.Based on each patient’s unique characteristics, more accurate dosages and drug selection can be made to achieve better therapeutic efficacy and less adverse reactions in precision medicine. A patient’s individual parameters that affect drug transporter action can be used to develop a precision medicine guidance, due to the fact that therapeutic efficacy and adverse reactions of drugs can both be affected by expression and function of drug transporters on the cell membrane surface. The purpose of this review is to summarize unique characteristics of human breast cancer resistant protein(BCRP) and the genetic variability in the BCRP encoded gene ABCG2 in the development of precision medicine. Inter-individual variability of BCRP/ABCG2 can impact choices and outcomes of drug treatment for several diseases, including cancer chemotherapy. Several factors have been implicated in expression and function of BCRP, including genetic, epigenetic, physiologic,pathologic, and environmental factors. Understanding the roles of these factors in controlling expression and function of BCRP is critical for the development of precision medicine based on BCRP-mediated drug transport.
基金This review article was supported by Connecticut Stem Cell Research Grant 11SCDIS02
文摘The host-dependent nature of idiosyncratic drug-induced liver injury(iDILI)suggests that rare genetic polymorphisms may contribute to the disease.Indeed,a few mutations in key genes have already been identified using conventional human genetics approaches.Over 50 commonly used drugs can precipitate iDILI,making this a substantial medical problem.Only recently have human induced pluripotent stem cells been used as a research tool to discover novel iDILI genes and to study the mechanisms of iDILI in vitro.Here we review the current state of stem cell use in the investigation of iDILI,with a special focus on genetics.In addition,the concerns and difficulties associated with genetics and animal model research are discussed.We then present the features of patient-specific pluripotent stem cells(which may be derived from iDILI patients themselves),and explain why these cells may be of great utility.A variety of recent approaches to produce hepatocyte-like cells from pluripotent cells and the associated advantages and limitations of such cells are discussed.Future directions for the use of stem cell science to investigate iDILI include novel ways to identify new iDILI genes,a consideration of epigenetic impacts on iDILI,and the development of new and improved strategies for the production of hepatocytes from human pluripotent cells.
