Skip to main content
SpringerLink
Log in

The Role of Pharmacogenomics in Individualized Medicine

  • Chapter
  • First Online:
Book cover Individualized Medicine

Part of the book series: Advances in Predictive, Preventive and Personalised Medicine ((APPPM,volume 7))

Abstract

Pharmacogenetics aims to use the patients’ genetic information in order to treat diseases more efficiently and minimize adverse events. The hereon based concept of Individualized Treatment finds its origin in associations of genetic information with treatment outcome. In this chapter a selection of gene-drug associations are summarized providing details on the underlying mechanisms, the clinical significance, and the current status of clinical implementation. The first example is the association between CYP2D6 and tamoxifen in the treatment of ER-positive breast cancer. A brief summary on the historical development of this research question provides insights in the strengths and difficulties of pharmacogenetics findings. In the context of the summary on the gene-drug association CYP2C19/clopidogrel the difficulties of the clinical implementation process, which have to be encountered, when including genetic testing in the every-day health care are mentioned. However, pharmacogenetics is not only a part of the post-marketing optimization of treatment outcome, but also plays an important role in drug development. Indeed, there are several examples where genetic findings were prerequisite for the following drug development and clinical approval. In this chapter the development of CCR5 antagonists and inhibitors of the bcr-abl tyrosine kinase are summarized. Finally, the novel drug ivacaftors, a drug specifically approved for a genetically defined minority of patients with cystic fibrosis, is mentioned in the context of pharmacogenetics.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Abe T, Kakyo M, Tokui T et al (1999) Identification of a novel gene family encoding human liver-specific organic anion transporter LST-1. J Biol Chem 274(24):17159–17163

    CAS  PubMed  Google Scholar 

  • Baccarani M, Deininger MW, Rosti G et al (2013) European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013. Blood 122(6):872–884

    CAS  PubMed  Google Scholar 

  • Balfour-Lynn IM (2014) Personalised medicine in cystic fibrosis is unaffordable. Paediatr Respir Rev 15(Suppl 1):2–5

    PubMed  Google Scholar 

  • Bang YJ, Van Cutsem E, Feyereislova A et al (2010) Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. The Lancet 376(9742):687–697

    CAS  Google Scholar 

  • Binkhorst L, Mathijssen RH, van Herk-Sukel MP et al (2013) Unjustified prescribing of CYP2D6 inhibiting SSRIs in women treated with tamoxifen. Breast Cancer Res Treat 139(3):923–929

    CAS  PubMed  Google Scholar 

  • Blanpain C, Libert F, Vassart G et al (2002) CCR5 and HIV infection. Receptors Channels 8(1):19–31

    CAS  PubMed  Google Scholar 

  • Bobadilla JL, Macek M Jr, Fine JP et al (2002) Cystic fibrosis: a worldwide analysis of CFTR mutations-correlation with incidence data and application to screening. Hum Mutat 19(6):575–606

    CAS  PubMed  Google Scholar 

  • Bofin AM, Ytterhus B, Martin C et al (2004) Detection and quantitation of HER-2 gene amplification and protein expression in breast carcinoma. Am J Clin Pathol 122(1):110–119

    CAS  PubMed  Google Scholar 

  • Bonanni B, Macis D, Maisonneuve P et al (2006) Polymorphism in the CYP2D6 tamoxifen-metabolizing gene influences clinical effect but not hot flashes: data from the Italian Tamoxifen Trial. J Clin Oncol 24(22):3708-3709 (author reply 3709)

    PubMed  Google Scholar 

  • Borges S, Desta Z, Li L et al (2006) Quantitative effect of CYP2D6 genotype and inhibitors on tamoxifen metabolism: implication for optimization of breast cancer treatment. Clin Pharmacol Ther 80(1):61–74

    CAS  PubMed  Google Scholar 

  • Brunton LL (ed) (2006) Goodman and Gilman’s the pharmacological basis of therapeutics. McGraw-Hill, New York

    Google Scholar 

  • Burstein HJ, Prestrud AA, Seidenfeld J et al (2010) American Society of Clinical Oncology clinical practice guideline: update on adjuvant endocrine therapy for women with hormone receptor-positive breast cancer. J Clin Oncol 28(23):3784–3796

    PubMed  Google Scholar 

  • Canestaro WJ, Austin MA, Thummel KE (2014) Genetic factors affecting statin concentrations and subsequent myopathy: a HuGENet systematic review. Genet Med. doi:10.1038/gim.2014.41

    Google Scholar 

  • Carlson B (2008) What the devil is personalized medicine? Biotechnol Healthc 5(1):17–19

    PubMed Central  PubMed  Google Scholar 

  • Carr DF, O’Meara H, Jorgensen AL et al (2013) SLCO1B1 genetic variant associated with statin-induced myopathy: a proof-of-concept study using the clinical practice research datalink. Clin Pharmacol Ther 94(6):695–701

    PubMed Central  CAS  PubMed  Google Scholar 

  • Chapman PB, Hauschild A, Robert C et al (2011) Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med 364(26):2507–2516

    PubMed Central  CAS  PubMed  Google Scholar 

  • Chubak J, Buist DS, Boudreau DM et al (2008) Breast cancer recurrence risk in relation to antidepressant use after diagnosis. Breast Cancer Res Treat 112(1):123–132

    PubMed Central  CAS  PubMed  Google Scholar 

  • Clancy JP, Johnson SG, Yee SW et al (2014) Clinical pharmacogenetics implementation consortium (CPIC) guidelines for ivacaftor therapy in the context of CFTR genotype. Clin Pharmacol Ther 95(6):592–597

    PubMed Central  CAS  PubMed  Google Scholar 

  • Corbin AS, Agarwal A, Loriaux M et al (2011) Human chronic myeloid leukemia stem cells are insensitive to imatinib despite inhibition of BCR-ABL activity. J Clin Invest 121(1):396–409

    PubMed Central  CAS  PubMed  Google Scholar 

  • Cortes JE, Talpaz M, Giles F et al (2003) Prognostic significance of cytogenetic clonal evolution in patients with chronic myelogenous leukemia on imatinib mesylate therapy. Blood 101(10):3794–3800

    CAS  PubMed  Google Scholar 

  • Crews KR, Gaedigk A, Dunnenberger HM et al (2014) Clinical pharmacogenetics implementation consortium guidelines for cytochrome P450 2D6 genotype and codeine therapy: 2014 update. Clin Pharmacol Ther 95(4):376–382

    PubMed Central  CAS  PubMed  Google Scholar 

  • Cronin-Fenton D, Lash TL, Sorensen HT (2010) Selective serotonin reuptake inhibitors and adjuvant tamoxifen therapy: risk of breast cancer recurrence and mortality. Future Onco 6(6):877–880

    CAS  Google Scholar 

  • Crossman LC, Druker BJ, Deininger MW et al (2005) hOCT 1 and resistance to imatinib. Blood 106(3):1133-1134 (author reply 1134)

    Google Scholar 

  • Daly AK (2014) Human leukocyte antigen (HLA) pharmacogenomic tests: potential and pitfalls. Curr Drug Metab 15(2):196–201

    CAS  PubMed  Google Scholar 

  • Daly AK, Donaldson PT, Bhatnagar P et al (2009) HLA-B*5701 genotype is a major determinant of drug-induced liver injury due to flucloxacillin. Nat Genet 41(7):816–819

    CAS  PubMed  Google Scholar 

  • Davies H, Bignell GR, Cox C et al (2002) Mutations of the BRAF gene in human cancer. Nature 417(6892):949–954

    CAS  PubMed  Google Scholar 

  • Deng H, Liu R, Ellmeier W et al (1996) Identification of a major co-receptor for primary isolates of HIV-1. Nature 381(6584):661–666

    CAS  PubMed  Google Scholar 

  • Desta Z, Ward BA, Soukhova NV et al (2004) Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther 310(3):1062–1075

    CAS  PubMed  Google Scholar 

  • Dieudonne AS, De Nys K, Casteels M et al (2014) How often did Belgian physicians co-prescribe tamoxifen with strong CYP2D6 inhibitors over the last 6 years? Acta Clin Belg 69(1):47–52

    CAS  PubMed  Google Scholar 

  • Drayna D (2005) Human taste genetics. Annu Rev Genomics Hum Genet 6:217–235

    CAS  PubMed  Google Scholar 

  • Druker BJ (2008) Translation of the Philadelphia chromosome into therapy for CML. Blood 112(13):4808–4817

    CAS  PubMed  Google Scholar 

  • Eichelbaum M, Spannbrucker N, Steincke B et al (1979) Defective N-oxidation of sparteine in man: a new pharmacogenetic defect. Eur J Clin Pharmacol 16(3):183–187

    CAS  PubMed  Google Scholar 

  • Este JA, Telenti A (2007) HIV entry inhibitors. The Lancet 370(9581):81–88

    CAS  Google Scholar 

  • Fann JR, Thomas-Rich AM, Katon WJ et al (2008) Major depression after breast cancer: a review of epidemiology and treatment. Gen Hosp Psychiatry 30(2):112–126

    PubMed  Google Scholar 

  • Feng Y, Broder CC, Kennedy PE et al (1996) HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science 272(5263):872–877

    CAS  PubMed  Google Scholar 

  • Ferrari M, Guasti L, Maresca A et al (2014) Association between statin-induced creatine kinase elevation and genetic polymorphisms in SLCO1B1, ABCB1 and ABCG2. Eur J Clin Pharmacol 70(5):539–547

    CAS  PubMed  Google Scholar 

  • Fox AL (1932) The relationship between chemical constitution and taste. Proc Natl Acad Sci U S A 18(1):115–120

    PubMed Central  CAS  PubMed  Google Scholar 

  • Gasche Y, Daali Y, Fathi M et al (2004) Codeine intoxication associated with ultrarapid CYP2D6 metabolism. N Engl J Med 351(27):2827–2831

    CAS  PubMed  Google Scholar 

  • Goetz MP, Rae JM, Suman VJ et al (2005) Pharmacogenetics of tamoxifen biotransformation is associated with clinical outcomes of efficacy and hot flashes. J Clin Oncol 23(36):9312–9318

    CAS  PubMed  Google Scholar 

  • Gong IY, Kim RB (2013) Impact of genetic variation in OATP transporters to drug disposition and response. Drug Metab Pharmacokinet 28(1):4–18

    CAS  PubMed  Google Scholar 

  • Harmsze AM, van Werkum JW, Hackeng CM et al (2012) The influence of CYP2C19*2 and *17 on on-treatment platelet reactivity and bleeding events in patients undergoing elective coronary stenting. Pharmacogenet Genomics 22(3):169–175

    CAS  PubMed  Google Scholar 

  • Hetherington S, McGuirk S, Powell G et al (2001) Hypersensitivity reactions during therapy with the nucleoside reverse transcriptase inhibitor abacavir. Clin Ther 23(10):1603–1614

    CAS  PubMed  Google Scholar 

  • Hetherington S, Hughes AR, Mosteller M et al (2002) Genetic variations in HLA-B region and hypersensitivity reactions to abacavir. The Lancet 359(9312):1121–1122

    CAS  Google Scholar 

  • Holmes DR Jr, Dehmer GJ, Kaul S et al (2010) ACCF/AHA clopidogrel clinical alert: approaches to the FDA “boxed warning”: a report of the American College of Cardiology Foundation Task Force on clinical expert consensus documents and the American Heart Association endorsed by the Society for Cardiovascular Angiography and Interventions and the Society of Thoracic Surgeons. J Am Coll Cardiol 56(4):321–341

    CAS  PubMed  Google Scholar 

  • Hughes DA, Vilar FJ, Ward CC et al (2004) Cost-effectiveness analysis of HLA B*5701 genotyping in preventing abacavir hypersensitivity. Pharmacogenetics 14(6):335–342

    PubMed  Google Scholar 

  • Hughes T, Deininger M, Hochhaus A et al (2006) Monitoring CML patients responding to treatment with tyrosine kinase inhibitors: review and recommendations for harmonizing current methodology for detecting BCR-ABL transcripts and kinase domain mutations and for expressing results. Blood 108(1):28–37

    PubMed Central  CAS  PubMed  Google Scholar 

  • Illing PT, Vivian JP, Dudek NL et al (2012) Immune self-reactivity triggered by drug-modified HLA-peptide repertoire. Nature 486(7404):554–558

    CAS  PubMed  Google Scholar 

  • Ingelman-Sundberg M, Sim SC, Gomez A et al (2007) Influence of cytochrome P450 polymorphisms on drug therapies: pharmacogenetic, pharmacoepigenetic and clinical aspects. Pharmacol Ther 116(3):496–526

    CAS  PubMed  Google Scholar 

  • Jabbour EJ, Cortes JE, Kantarjian HM (2013) Resistance to tyrosine kinase inhibition therapy for chronic myelogenous leukemia: a clinical perspective and emerging treatment options. Clin Lymphoma Myeloma Leuk 13(5):515–529

    PubMed Central  CAS  PubMed  Google Scholar 

  • Jin Y, Desta Z, Stearns V et al (2005) CYP2D6 genotype, antidepressant use, and tamoxifen metabolism during adjuvant breast cancer treatment. J Natl Cancer Inst 97(1):30–39

    CAS  PubMed  Google Scholar 

  • Kalliokoski A, Niemi M (2009) Impact of OATP transporters on pharmacokinetics. Br J Pharmacol 158(3):693–705

    PubMed Central  CAS  PubMed  Google Scholar 

  • Kelly CM, Juurlink DN, Gomes T et al (2010) Selective serotonin reuptake inhibitors and breast cancer mortality in women receiving tamoxifen: a population based cohort study. Bmj 340:c693

    Google Scholar 

  • Kim UK, Breslin PA, Reed D et al (2004) Genetics of human taste perception. J Dent Res 83(6):448–453

    PubMed  Google Scholar 

  • Kiyotani K, Mushiroda T, Imamura CK et al (2010) Significant effect of polymorphisms in CYP2D6 and ABCC2 on clinical outcomes of adjuvant tamoxifen therapy for breast cancer patients. J Clin Oncol 28(8):1287–1293

    CAS  PubMed  Google Scholar 

  • Klein DJ, Thorn CF, Desta Z et al (2013) PharmGKB summary: tamoxifen pathway, pharmacokinetics. Pharmacogenet Genomics 23(11):643–647

    PubMed Central  CAS  PubMed  Google Scholar 

  • Lash TL, Cronin-Fenton D, Ahern TP et al (2010) Breast cancer recurrence risk related to concurrent use of SSRI antidepressants and tamoxifen. Acta Oncol 49(3):305–312

    PubMed Central  CAS  PubMed  Google Scholar 

  • Lau A, Seiter K (2014) Second-line therapy for patients with chronic myeloid leukemia resistant to first-line imatinib. Clin Lymphoma Myeloma Leuk 14(3):186–196

    PubMed  Google Scholar 

  • Li S, Li D (2007) Stem cell and kinase activity-independent pathway in resistance of leukaemia to BCR-ABL kinase inhibitors. J Cell Mol Med 11(6):1251–1262

    CAS  PubMed  Google Scholar 

  • Li SG, Li L (2013) Targeted therapy in HER2-positive breast cancer. Biomed Rep 1(4):499–505

    PubMed Central  CAS  PubMed  Google Scholar 

  • Lim YC, Desta Z, Flockhart DA et al (2005) Endoxifen (4-hydroxy-N-desmethyl-tamoxifen) has anti-estrogenic effects in breast cancer cells with potency similar to 4-hydroxy-tamoxifen. Cancer Chemother Pharmacol 55(5):471–478

    CAS  PubMed  Google Scholar 

  • Lim HS, Ju Lee H, Seok Lee K et al (2007) Clinical implications of CYP2D6 genotypes predictive of tamoxifen pharmacokinetics in metastatic breast cancer. J Clin Oncol 25(25):3837–3845

    CAS  PubMed  Google Scholar 

  • Lin NH, Kuritzkes DR (2009) Tropism testing in the clinical management of HIV-1 infection. Curr Opin HIV AIDS 4(6):481–487

    PubMed Central  PubMed  Google Scholar 

  • Link E, Parish S, Armitage J et al (2008) SLCO1B1 variants and statin-induced myopathy—a genomewide study. N Engl J Med 359(8):789–799

    CAS  PubMed  Google Scholar 

  • LoRusso PM, Weiss D, Guardino E et al (2011) Trastuzumab emtansine: a unique antibody-drug conjugate in development for human epidermal growth factor receptor 2-positive cancer. Clin Cancer Res 17(20):6437–6447

    CAS  PubMed  Google Scholar 

  • Lotsch J, Rohrbacher M, Schmidt H et al (2009) Can extremely low or high morphine formation from codeine be predicted prior to therapy initiation? Pain 144(1-2):119–124

    PubMed  Google Scholar 

  • Ma Q, Lu AY (2011) Pharmacogenetics, pharmacogenomics, and individualized medicine. Pharmacol Rev 63(2):437–459

    CAS  PubMed  Google Scholar 

  • Maeda K, Das D, Nakata H et al (2012) CCR5 inhibitors: emergence, success, and challenges. Expert Opin Emerg Drugs 17(2):135–145

    CAS  PubMed  Google Scholar 

  • Mahgoub A, Idle JR, Dring LG et al (1977) Polymorphic hydroxylation of Debrisoquine in man. Lancet 2(8038):584–586

    CAS  PubMed  Google Scholar 

  • Mallal S, Nolan D, Witt C et al (2002) Association between presence of HLA-B*5701, HLA-DR7, and HLA-DQ3 and hypersensitivity to HIV-1 reverse-transcriptase inhibitor abacavir. Lancet 359(9308):727–732

    CAS  PubMed  Google Scholar 

  • Manolio TA (2013) Bringing genome-wide association findings into clinical use. Nat Rev Genet 14(8):549–558

    CAS  PubMed  Google Scholar 

  • Mauro MJ, Druker BJ (2001a) STI571: targeting BCR-ABL as therapy for CML. Oncologist 6(3):233–238

    Google Scholar 

  • Mauro MJ, Druker BJ (2001b) STI571: a gene product-targeted therapy for leukemia. Curr Oncol Rep 3(3):223–227

    Google Scholar 

  • McKeage K, Perry CM (2002) Trastuzumab: a review of its use in the treatment of metastatic breast cancer overexpressing HER2. Drugs 62(1):209–243

    CAS  PubMed  Google Scholar 

  • Meyer zu Schwabedissen HE, Kim RB (2009) Hepatic OATP1B transporters and nuclear receptors PXR and CAR: interplay, regulation of drug disposition genes, and single nucleotide polymorphisms. Mol Pharm 6(6):1644–1661

    CAS  PubMed  Google Scholar 

  • Nowell SA, Ahn J, Rae JM et al (2005) Association of genetic variation in tamoxifen-metabolizing enzymes with overall survival and recurrence of disease in breast cancer patients. Breast Cancer Res Treat 91(3):249–258

    CAS  PubMed  Google Scholar 

  • O’Sullivan BP, Orenstein DM, Milla CE (2013) Pricing for orphan drugs: will the market bear what society cannot? Jama 310(13):1343–1344

    PubMed  Google Scholar 

  • Owen RP, Sangkuhl K, Klein TE et al (2009) Cytochrome P450 2D6. Pharmacogenet Genomics 19(7):559–562

    CAS  PubMed  Google Scholar 

  • Pacanowski MA, Leptak C, Zineh I (2014) Next-generation medicines: past regulatory experience and considerations for the future. Clin Pharmacol Ther 95(3):247–249

    CAS  PubMed  Google Scholar 

  • Pare G, Eikelboom JW, Sibbing D et al (2011) Testing should not be done in all patients treated with clopidogrel who are undergoing percutaneous coronary intervention. Circ Cardiovasc Interv 4(5):514-521. (discussion 521)

    PubMed  Google Scholar 

  • Perez EA, Cortes J, Gonzalez-Angulo AM et al (2014) HER2 testing: current status and future directions. Cancer Treat Rev 40(2):276–284

    CAS  PubMed  Google Scholar 

  • Phillips EJ, Mallal SA (2013) HLA-B*5701 and flucloxacillin associated drug-induced liver disease. Aids 27(3):491–492

    PubMed  Google Scholar 

  • Province MA, Goetz MP, Brauch H et al (2014) CYP2D6 genotype and adjuvant tamoxifen: meta-analysis of heterogeneous study populations. Clin Pharmacol Ther 95(2):216–227

    PubMed Central  CAS  PubMed  Google Scholar 

  • Pulley JM, Denny JC, Peterson JF et al (2012) Operational implementation of prospective genotyping for personalized medicine: the design of the Vanderbilt PREDICT project. Clin Pharmacol Ther 92(1):87–95

    PubMed Central  CAS  PubMed  Google Scholar 

  • Quintas-Cardama A, Cortes J (2009) Molecular biology of bcr-abl1-positive chronic myeloid leukemia. Blood 113(8):1619–1630

    PubMed Central  CAS  PubMed  Google Scholar 

  • Rae JM, Drury S, Hayes DF et al (2012) CYP2D6 and UGT2B7 genotype and risk of recurrence in tamoxifen-treated breast cancer patients. J Natl Cancer Inst 104(6):452–460

    PubMed Central  CAS  PubMed  Google Scholar 

  • Rauch A, Nolan D, Martin A et al (2006) Prospective genetic screening decreases the incidence of abacavir hypersensitivity reactions in the Western Australian HIV cohort study. Clin Infect Dis 43(1):99–102

    CAS  PubMed  Google Scholar 

  • Regan MM, Leyland-Jones B, Bouzyk M et al (2012) CYP2D6 genotype and tamoxifen response in postmenopausal women with endocrine-responsive breast cancer: the breast international group 1-98 trial. J Natl Cancer Inst 104(6):441–451

    PubMed Central  CAS  PubMed  Google Scholar 

  • Reynolds K, Sarangi S, Bardia A et al (2014) Precision medicine and personalized breast cancer: combination pertuzumab therapy. Pharmgenomics Pers Med 7:95–105

    PubMed Central  PubMed  Google Scholar 

  • Riordan JR (2008) CFTR function and prospects for therapy. Annu Rev Biochem 77:701–726

    CAS  PubMed  Google Scholar 

  • Roberts JD, Wells GA, Le May MR et al (2012) Point-of-care genetic testing for personalisation of antiplatelet treatment (RAPID GENE): a prospective, randomised, proof-of-concept trial. The Lancet 379(9827):1705–1711

    CAS  Google Scholar 

  • Rudkin CT, Hungerford DA, Nowell PC (1964) DNA contents of chromosome Ph1 and chromosome 21 in human chronic granulocytic leukemia. Science 144(3623):1229–1231

    CAS  PubMed  Google Scholar 

  • Samson M, Libert F, Doranz BJ et al (1996) Resistance to HIV-1 infection in caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene. Nature 382(6593):722–725

    CAS  PubMed  Google Scholar 

  • Sass AE, Neufeld EJ (2002) Risk factors for thromboembolism in teens: when should I test? Curr Opin Pediatr 14(4):370–378

    PubMed  Google Scholar 

  • Schroth W, Antoniadou L, Fritz P et al (2007) Breast cancer treatment outcome with adjuvant tamoxifen relative to patient CYP2D6 and CYP2C19 genotypes. J Clin Oncol 25(33):5187–5193

    CAS  PubMed  Google Scholar 

  • Schroth W, Goetz MP, Hamann U et al (2009) Association between CYP2D6 polymorphisms and outcomes among women with early stage breast cancer treated with tamoxifen. Jama 302(13):1429–1436

    PubMed Central  CAS  PubMed  Google Scholar 

  • Scott SA, Sangkuhl K, Gardner EE et al (2011) Clinical Pharmacogenetics Implementation Consortium guidelines for cytochrome P450-2C19 (CYP2C19) genotype and clopidogrel therapy. Clin Pharmacol Ther 90(2):328–332

    PubMed Central  CAS  PubMed  Google Scholar 

  • Shahin MH, Johnson JA (2013) Clopidogrel and warfarin pharmacogenetic tests: what is the evidence for use in clinical practice? Curr Opin Cardiol 28(3):305–314

    PubMed Central  PubMed  Google Scholar 

  • Shuldiner AR, Palmer K, Pakyz RE et al (2014) Implementation of pharmacogenetics: the university of Maryland personalized anti-platelet pharmacogenetics program. Am J Med Genet C Semin Med Genet 166C(1):76–84

    PubMed  Google Scholar 

  • Sibbing D, Bernlochner I, Kastrati A et al (2011) Current evidence for genetic testing in clopidogrel-treated patients undergoing coronary stenting. Circ Cardiovasc Interv 4(5):505-513 (discussion 513)

    PubMed  Google Scholar 

  • Siller-Matula JM, Trenk D, Schror K et al (2013) Response variability to P2Y12 receptor inhibitors: expectations and reality. JACC Cardiovasc Interv 6(11):1111–1128

    PubMed  Google Scholar 

  • Slamon DJ, Clark GM, Wong SG et al (1987) Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235(4785):177–182

    CAS  PubMed  Google Scholar 

  • Sosnay PR, Siklosi KR, Van Goor F et al (2013) Defining the disease liability of variants in the cystic fibrosis transmembrane conductance regulator gene. Nat Genet 45(10):1160–1167

    CAS  PubMed  Google Scholar 

  • Stearns V, Johnson MD, Rae JM et al (2003) Active tamoxifen metabolite plasma concentrations after coadministration of tamoxifen and the selective serotonin reuptake inhibitor paroxetine. J Natl Cancer Inst 95(23):1758–1764

    CAS  PubMed  Google Scholar 

  • Stewart A (2013) SLCO1B1 Polymorphisms and Statin-Induced Myopathy. PLoS Curr 5. doi:10.1371/currents.eogt.d21e7f0c58463571bb0d9d3a19b82203

    Google Scholar 

  • Stimpfle F, Karathanos A, Droppa M et al (2014) Impact of point-of-care testing for CYP2C19 on platelet inhibition in patients with acute coronary syndrome and early dual antiplatelet therapy in the emergency setting. Thromb Res 134(1):105–110

    CAS  PubMed  Google Scholar 

  • Stingl Kirchheiner JC, Brockmöller J (2011) Why, when, and how should pharmacogenetics be applied in clinical studies?: current and future approaches to study designs. Clin Pharmacol Ther 89(2):198–209

    CAS  PubMed  Google Scholar 

  • Tafe LJ, Tsongalis GJ (2012) The human epidermal growth factor receptor 2 (HER2). Clin Chem Lab Med 50(1):23–30

    CAS  Google Scholar 

  • Thorn CF, Klein TE, Altman RB (2009) Codeine and morphine pathway. Pharmacogenet Genomics 19(7):556–558

    CAS  PubMed  Google Scholar 

  • Tirona RG, Leake BF, Merino G et al (2001) Polymorphisms in OATP-C: identification of multiple allelic variants associated with altered transport activity among European- and African-Americans. J Biol Chem 276(38):35669–35675

    CAS  PubMed  Google Scholar 

  • Trenk D, Hochholzer W (2014) Genetics of platelet inhibitor treatment. Br J Clin Pharmacol 77(4):642–653

    CAS  PubMed  Google Scholar 

  • Turner RM, Pirmohamed M (2014) Cardiovascular pharmacogenomics: expectations and practical benefits. Clin Pharmacol Ther 95(3):281–293

    CAS  PubMed  Google Scholar 

  • Vultur A, Villanueva J, Herlyn M (2011) Targeting BRAF in advanced melanoma: a first step toward manageable disease. Clin Cancer Res 17(7):1658–1663

    PubMed Central  CAS  PubMed  Google Scholar 

  • Wegman P, Vainikka L, Stal O et al (2005) Genotype of metabolic enzymes and the benefit of tamoxifen in postmenopausal breast cancer patients. Breast Cancer Res 7(3):R284–R290

    PubMed Central  CAS  PubMed  Google Scholar 

  • Wegman P, Elingarami S, Carstensen J et al (2007) Genetic variants of CYP3A5, CYP2D6, SULT1A1, UGT2B15 and tamoxifen response in postmenopausal patients with breast cancer. Breast Cancer Res 9(1):R7

    PubMed Central  PubMed  Google Scholar 

  • Weitzel KW, Elsey AR, Langaee TY et al (2014) Clinical pharmacogenetics implementation: approaches, successes, and challenges. Am J Med Genet C Semin Med Genet 166C(1):56–67

    PubMed  Google Scholar 

  • Whiting P, Al M, Burgers L et al (2014) Ivacaftor for the treatment of patients with cystic fibrosis and the G551D mutation: a systematic review and cost-effectiveness analysis. Health Technol Assess 18(18):1–106

    Google Scholar 

  • Wilke RA, Ramsey LB, Johnson SG et al (2012) The clinical pharmacogenomics implementation consortium: CPIC guideline for SLCO1B1 and simvastatin-induced myopathy. Clin Pharmacol Ther 92(1):112–117

    PubMed Central  CAS  PubMed  Google Scholar 

  • Wright RS, Anderson JL, Adams CD et al (2011) 2011 ACCF/AHA focused update of the guidelines for the management of patients with unstable angina/Non-ST-elevation myocardial infarction (updating the 2007 guideline): a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation 123(18):2022–2060

    PubMed  Google Scholar 

  • Xie X, Ma YT, Yang YN et al (2013) Personalized antiplatelet therapy according to CYP2C19 genotype after percutaneous coronary intervention: a randomized control trial. Int J Cardiol 168(4):3736–3740

    PubMed  Google Scholar 

  • Yang W, Raufi A, Klempner SJ (2014) Targeted therapy for gastric cancer: molecular pathways and ongoing investigations. Biochim Biophys Acta. doi: 10.1016/j.bbcan.2014.05.003

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departement Pharmazeutische Wissenschaften, Biopharmazie, Universität Basel, Kingelbergstr. 50, 4056, Basel, Switzerland

    Henriette E. Meyer zu Schwabedissen

Authors
  1. Henriette E. Meyer zu Schwabedissen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Henriette E. Meyer zu Schwabedissen .

Editor information

Editors and Affiliations

  1. University Medicine Greifswald, Department for Ethics, Theory and History in Life Sciences, Greifswald, Germany

    Tobias Fischer

  2. University of Greifswald, GANI_MED – Greifswald Approach to Individualized Medicine, Greifswald, Germany

    Martin Langanke

  3. University of Greifswald, GANI_MED – Greifswald Approach to Individualized Medicine, Greifswald, Germany

    Paul Marschall

  4. University Medicine of Johannes Gutenberg-University Mainz, Institute for History, Theory and Ethic of Medicine, Mainz, Germany

    Susanne Michl

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Meyer zu Schwabedissen, H. (2015). The Role of Pharmacogenomics in Individualized Medicine. In: Fischer, T., Langanke, M., Marschall, P., Michl, S. (eds) Individualized Medicine. Advances in Predictive, Preventive and Personalised Medicine, vol 7. Springer, Cham. https://doi.org/10.1007/978-3-319-11719-5_7

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-11719-5_7

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-11718-8

  • Online ISBN: 978-3-319-11719-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation