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.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
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
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
Balfour-Lynn IM (2014) Personalised medicine in cystic fibrosis is unaffordable. Paediatr Respir Rev 15(Suppl 1):2–5
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
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
Blanpain C, Libert F, Vassart G et al (2002) CCR5 and HIV infection. Receptors Channels 8(1):19–31
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
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
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)
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
Brunton LL (ed) (2006) Goodman and Gilman’s the pharmacological basis of therapeutics. McGraw-Hill, New York
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
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
Carlson B (2008) What the devil is personalized medicine? Biotechnol Healthc 5(1):17–19
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
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
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
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
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
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
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
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
Crossman LC, Druker BJ, Deininger MW et al (2005) hOCT 1 and resistance to imatinib. Blood 106(3):1133-1134 (author reply 1134)
Daly AK (2014) Human leukocyte antigen (HLA) pharmacogenomic tests: potential and pitfalls. Curr Drug Metab 15(2):196–201
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
Davies H, Bignell GR, Cox C et al (2002) Mutations of the BRAF gene in human cancer. Nature 417(6892):949–954
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
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
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
Drayna D (2005) Human taste genetics. Annu Rev Genomics Hum Genet 6:217–235
Druker BJ (2008) Translation of the Philadelphia chromosome into therapy for CML. Blood 112(13):4808–4817
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
Este JA, Telenti A (2007) HIV entry inhibitors. The Lancet 370(9581):81–88
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
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
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
Fox AL (1932) The relationship between chemical constitution and taste. Proc Natl Acad Sci U S A 18(1):115–120
Gasche Y, Daali Y, Fathi M et al (2004) Codeine intoxication associated with ultrarapid CYP2D6 metabolism. N Engl J Med 351(27):2827–2831
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
Gong IY, Kim RB (2013) Impact of genetic variation in OATP transporters to drug disposition and response. Drug Metab Pharmacokinet 28(1):4–18
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
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
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
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
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
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
Illing PT, Vivian JP, Dudek NL et al (2012) Immune self-reactivity triggered by drug-modified HLA-peptide repertoire. Nature 486(7404):554–558
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
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
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
Kalliokoski A, Niemi M (2009) Impact of OATP transporters on pharmacokinetics. Br J Pharmacol 158(3):693–705
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
Kim UK, Breslin PA, Reed D et al (2004) Genetics of human taste perception. J Dent Res 83(6):448–453
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
Klein DJ, Thorn CF, Desta Z et al (2013) PharmGKB summary: tamoxifen pathway, pharmacokinetics. Pharmacogenet Genomics 23(11):643–647
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
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
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
Li SG, Li L (2013) Targeted therapy in HER2-positive breast cancer. Biomed Rep 1(4):499–505
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
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
Lin NH, Kuritzkes DR (2009) Tropism testing in the clinical management of HIV-1 infection. Curr Opin HIV AIDS 4(6):481–487
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
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
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
Ma Q, Lu AY (2011) Pharmacogenetics, pharmacogenomics, and individualized medicine. Pharmacol Rev 63(2):437–459
Maeda K, Das D, Nakata H et al (2012) CCR5 inhibitors: emergence, success, and challenges. Expert Opin Emerg Drugs 17(2):135–145
Mahgoub A, Idle JR, Dring LG et al (1977) Polymorphic hydroxylation of Debrisoquine in man. Lancet 2(8038):584–586
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
Manolio TA (2013) Bringing genome-wide association findings into clinical use. Nat Rev Genet 14(8):549–558
Mauro MJ, Druker BJ (2001a) STI571: targeting BCR-ABL as therapy for CML. Oncologist 6(3):233–238
Mauro MJ, Druker BJ (2001b) STI571: a gene product-targeted therapy for leukemia. Curr Oncol Rep 3(3):223–227
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
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
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
O’Sullivan BP, Orenstein DM, Milla CE (2013) Pricing for orphan drugs: will the market bear what society cannot? Jama 310(13):1343–1344
Owen RP, Sangkuhl K, Klein TE et al (2009) Cytochrome P450 2D6. Pharmacogenet Genomics 19(7):559–562
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
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)
Perez EA, Cortes J, Gonzalez-Angulo AM et al (2014) HER2 testing: current status and future directions. Cancer Treat Rev 40(2):276–284
Phillips EJ, Mallal SA (2013) HLA-B*5701 and flucloxacillin associated drug-induced liver disease. Aids 27(3):491–492
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
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
Quintas-Cardama A, Cortes J (2009) Molecular biology of bcr-abl1-positive chronic myeloid leukemia. Blood 113(8):1619–1630
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
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
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
Reynolds K, Sarangi S, Bardia A et al (2014) Precision medicine and personalized breast cancer: combination pertuzumab therapy. Pharmgenomics Pers Med 7:95–105
Riordan JR (2008) CFTR function and prospects for therapy. Annu Rev Biochem 77:701–726
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
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
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
Sass AE, Neufeld EJ (2002) Risk factors for thromboembolism in teens: when should I test? Curr Opin Pediatr 14(4):370–378
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
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
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
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
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
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)
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
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
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
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
Stewart A (2013) SLCO1B1 Polymorphisms and Statin-Induced Myopathy. PLoS Curr 5. doi:10.1371/currents.eogt.d21e7f0c58463571bb0d9d3a19b82203
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
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
Tafe LJ, Tsongalis GJ (2012) The human epidermal growth factor receptor 2 (HER2). Clin Chem Lab Med 50(1):23–30
Thorn CF, Klein TE, Altman RB (2009) Codeine and morphine pathway. Pharmacogenet Genomics 19(7):556–558
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
Trenk D, Hochholzer W (2014) Genetics of platelet inhibitor treatment. Br J Clin Pharmacol 77(4):642–653
Turner RM, Pirmohamed M (2014) Cardiovascular pharmacogenomics: expectations and practical benefits. Clin Pharmacol Ther 95(3):281–293
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
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
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
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
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
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
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
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
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
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights 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)