Pharmacogenomics: Bench to bedside.

Extract: Pharmacogenetics is the study of how genetic inheritance affects a person's response to drugs. A major goal for pharmacogenetic research has been the individualization of drug therapy, by which doctors could more precisely cater to an individual's physiological particularities when prescribing drugs, which would both maximize efficacy and minimize toxicity. Advances in pharmacogenetics have converged with rapid developments in human genomics; as a result, pharmacogenetics has evolved into pharmacogenomics. We will briefly review the development of pharmacogenetics and pharmacogenomics, and outline factors that have influenced the "translation" of pharmacogenomics from the research bench to the patients' bedside. The end of the 20th and beginning of the 21st centuries saw the "therapeutic revolution" (which had resulted in the development of drugs to treat diseases ranging from hypertension to childhood leukemia) converge with the "genomic revolution."

[1]  L. Lennard.  The clinical pharmacology of 6-mercaptopurine , 2005, European Journal of Clinical Pharmacology.

[2]  L. Lesko,et al.  Pharmacogenomic data: FDA voluntary and required submission guidance. , 2004, Pharmacogenomics.

[3]  John K Leighton,et al.  Pharmacogenomic data submissions to the FDA: non-clinical case studies. , 2004, Pharmacogenomics.

[4]  Pharmacogenomic data submissions to the FDA: clinical case studies. , 2004, Pharmacogenomics.

[5]  Pharmacogenomic data submissions to the FDA: clinical pharmacology case studies. , 2004, Pharmacogenomics.

[6]  Michel Eichelbaum,et al.  Comprehensive analysis of thiopurine S-methyltransferase phenotype-genotype correlation in a large population of German-Caucasians and identification of novel TPMT variants. , 2004, Pharmacogenetics.

[7]  S. Gabriel,et al.  EGFR Mutations in Lung Cancer: Correlation with Clinical Response to Gefitinib Therapy , 2004, Science.

[8]  M. Ratain,et al.  “Irinogenetics” and UGT1A: from Genotypes to Haplotypes , 2004, Clinical pharmacology and therapeutics.

[9]  Patricia L. Harris,et al.  Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. , 2004, The New England journal of medicine.

[10]  R. Weinshilboum,et al.  Pharmacogenetics: Inherited Variation in Amino Acid Sequence and Altered Protein Quantity , 2004, Clinical pharmacology and therapeutics.

[11]  M. Eichelbaum,et al.  Defective N-oxidation of sparteine in man: A new pharmacogenetic defect , 1979, European Journal of Clinical Pharmacology.

[12]  R. Altman,et al.  PharmGKB: the pharmacogenetics and pharmacogenomics knowledge base. , 2005, Methods in molecular biology.

[13]  Toshihiro Tanaka.  The International HapMap Project , 2003, Nature.

[14]  David B. Goldstein,et al.  Pharmacogenetics goes genomic , 2003, Nature Reviews Genetics.

[15]  E. Zerhouni.  The NIH Roadmap , 2003, Science.

[16]  F. Collins,et al.  Welcome to the genomic era. , 2003, The New England journal of medicine.

[17]  R. Weinshilboum,et al.  Thiopurine S-methyltransferase pharmacogenetics: chaperone protein association and allozyme degradation. , 2003, Pharmacogenetics.

[18]  E. Clayton.  Ethical, legal, and social implications of genomic medicine. , 2003, The New England journal of medicine.

[19]  R. Weinshilboum.  Inheritance and drug response. , 2003, The New England journal of medicine.

[20]  D. Nebert,et al.  Pharmacogenomics and “Individualized Drug Therapy” , 2003 .

[21]  P. Bosma.  Inherited disorders of bilirubin metabolism. , 2003, Journal of hepatology.

[22]  Allen D. Roses,et al.  Genome-based pharmacogenetics and the pharmaceutical industry , 2002, Nature Reviews Drug Discovery.

[23]  M. Ingelman-Sundberg,et al.  Unravelling the functional genomics of the human CYP2D6 gene locus. , 2001, Pharmacogenetics.

[24]  T. Fleming,et al.  Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. , 2001, The New England journal of medicine.

[25]  E. Eisenhauer.  From the molecule to the clinic--inhibiting HER2 to treat breast cancer. , 2001, The New England journal of medicine.

[26]  Timothy B. Stockwell,et al.  The Sequence of the Human Genome , 2001, Science.

[27]  J. V. Moran,et al.  Initial sequencing and analysis of the human genome. , 2001, Nature.

[28]  I. Hall,et al.  Pharmacogenetics of asthma. , 2000, The European respiratory journal.

[29]  J. Brockmöller,et al.  Arylamine N-acetyltransferase activity in man. , 1999, Drug metabolism reviews.

[30]  F. Collins,et al.  Shattuck lecture--medical and societal consequences of the Human Genome Project. , 1999, The New England journal of medicine.

[31]  Nicholas Schork,et al.  Pharmacogenetic association between ALOX5 promoter genotype and the response to anti-asthma treatment , 1999, Nature Genetics.

[32]  D. Collier,et al.  The frequency and distribution of thiopurine methyltransferase alleles in Caucasian and Asian populations. , 1999, Pharmacogenetics.

[33]  W. Evans,et al.  Enhanced proteolysis of thiopurine S-methyltransferase (TPMT) encoded by mutant alleles in humans (TPMT*3A, TPMT*2): mechanisms for the genetic polymorphism of TPMT activity. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[34]  M Ingelman-Sundberg,et al.  Frequent distribution of ultrarapid metabolizers of debrisoquine in an ethiopian population carrying duplicated and multiduplicated functional CYP2D6 alleles. , 1996, The Journal of pharmacology and experimental therapeutics.

[35]  B. Burchell,et al.  Genetic variation in bilirubin UDP-glucuronosyltransferase gene promoter and Gilbert's syndrome , 1996, The Lancet.

[36]  R. Weinshilboum,et al.  Thiopurine methyltransferase pharmacogenetics: human gene cloning and characterization of a common polymorphism. , 1996, DNA and cell biology.

[37]  S. Sindrup,et al.  The pharmacogenetics of codeine hypoalgesia. , 1995, Pharmacogenetics.

[38]  D Lindhout,et al.  The genetic basis of the reduced expression of bilirubin UDP-glucuronosyltransferase 1 in Gilbert's syndrome. , 1995, The New England journal of medicine.

[39]  H K Kroemer,et al.  "It's the genes, stupid". Molecular bases and clinical consequences of genetic cytochrome P450 2D6 polymorphism. , 1995, Life sciences.

[40]  P. Evans,et al.  Genetic Factors in Drug Therapy: Clinical and Molecular Pharmacogenetics , 1994 .

[41]  M. Ingelman-Sundberg,et al.  Inherited amplification of an active gene in the cytochrome P450 CYP2D locus as a cause of ultrarapid metabolism of debrisoquine. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[42]  J. Gummert,et al.  Azathioprine-induced myelosuppression in thiopurine methyltransferase deficient heart transplant recipient , 1993, The Lancet.

[43]  L. Bertilsson,et al.  Pronounced differences between native Chinese and Swedish populations in the polymorphic hydroxylations of debrisoquin and S‐mephenytoin , 1992, Clinical pharmacology and therapeutics.

[44]  U. Meyer,et al.  Polymorphic formation of morphine from codeine in poor and extensive metabolizers of dextromethorphan: Relationship to the presence of immunoidentified cytochrome P‐450IID1 , 1990, Clinical pharmacology and therapy.

[45]  R. Weinshilboum,et al.  Pharmacogenetics of acute azathioprine toxicity: Relationship to thiopurine methyltransferase genetic polymorphism , 1989, Clinical pharmacology and therapeutics.

[46]  D. Nebert,et al.  Human debrisoquine 4-hydroxylase (P450IID1): cDNA and deduced amino acid sequence and assignment of the CYP2D locus to chromosome 22. , 1988, Genomics.

[47]  R. Weinshilboum.  The therapeutic revolution , 1987, Clinical pharmacology and therapeutics.

[48]  R. Weinshilboum,et al.  Human kidney thiopurine methyltransferase. Purification and biochemical properties. , 1983, Biochemical pharmacology.

[49]  R. Weinshilboum,et al.  Pharmacogenetics of human thiopurine methyltransferase: kidney-erythrocyte correlation and immunotitration studies. , 1982, The Journal of pharmacology and experimental therapeutics.

[50]  J. Timbrell,et al.  Polymorphic acetylation of hydralazine , 1980, Clinical pharmacology and therapeutics.

[51]  R. Weinshilboum,et al.  Mercaptopurine pharmacogenetics: monogenic inheritance of erythrocyte thiopurine methyltransferase activity. , 1980, American journal of human genetics.

[52]  W. Kalow.  Pharmacogenetics of drug metabolism , 1980 .

[53]  J. Oates,et al.  Effect of acetylator phenotype on the rate at which procainamide induces antinuclear antibodies and the lupus syndrome. , 1978, The New England journal of medicine.

[54]  J. Idle,et al.  POLYMORPHIC HYDROXYLATION OF DEBRISOQUINE IN MAN , 1977, The Lancet.

[55]  D. Drayer,et al.  Clinical consequences of polymorphic acetylation of basic drugs , 1977, Clinical pharmacology and therapeutics.

[56]  D. Drayer,et al.  Polymorphic acetylation of procainamide in man , 1975, Clinical pharmacology and therapeutics.

[57]  H. Perry,et al.  Relationship of acetyl transferase activity to antinuclear antibodies and toxic symptoms in hypertensive patients treated with hydralazine. , 1970, The Journal of laboratory and clinical medicine.

[58]  E. Vesell,et al.  Genetic control of dicumarol levels in man. , 1968, The Journal of clinical investigation.

[59]  E. Vesell,et al.  Genetic Control of Drug Levels in Man: Antipyrine , 1968, Science.

[60]  C. Remy.  Metabolism of thiopyrimidines and thiopurines. S-Methylation with S-adenosylmethionine transmethylase and catabolism in mammalian tissues. , 1963, The Journal of biological chemistry.

[61]  W. Kalow.  Pharmacogenetics : heredity and the response to drugs , 1962 .

[62]  V. McKusick,et al.  Genetic Control of Isoniazid Metabolism in Man , 1960, British medical journal.

[63]  L. Goodman,et al.  THE PHARMACOLOGICAL BASIS OF THERAPEUTICS , 1966 .