Personalized medicine

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Personalized medicine or PM (aspects of which may also be referred to as precision medicine) is a medical model that proposes the customization of healthcare - with medical decisions, practices, and/or products being tailored to the individual patient. In this model, diagnostic testing is often employed for selecting appropriate therapies; terms used to describe some of these tests include "companion diagnostics" or "theranostics." Customized therapeutic products themselves can fall under PM as well. The use of genetic information has played a major role in certain aspects of personalized medicine (e.g. pharmacogenomics, therapygenetics), and the term was even first coined in the context of genetics (though it has since broadened to encompass all sorts of personalization measures).[1]

To distinguish from the sense in which medicine has always been inherently "personal" to each patient, PM commonly denotes the use of some kind of technology or discovery enabling a level of personalization not previously feasible or practical.


Traditional clinical diagnosis and management focuses on the individual patient's clinical signs and symptoms, medical and family history, and data from laboratory and imaging evaluation to diagnose and treat illnesses. This is often a reactive approach to treatment, i.e., treatment/medication starts after the signs and symptoms appear.

Advances in medical genetics and human genetics have enabled a more detailed understanding of the impact of genetics in disease. Large collaborative research projects (for example, the Human genome project) have laid the groundwork for the understanding of the roles of genes in normal human development and physiology, revealed single nucleotide polymorphisms (SNPs) that account for some of the genetic variability between individuals, and made possible the use of genome-wide association studies (GWAS) to examine genetic variation and risk for many common diseases.[1]

Beyond germline genetics, molecular pathology is a much wider open area for therapeutic and preventive applications. Inter-personal difference of molecular pathology is diverse, so as inter-personal difference in the exposome, which influence disease processes through the interactome within the tissue microenvironment, differentially from person to person.[1] As the theoretical basis of personalized medicine, the "unique disease principle"

[2] (which was first described in neoplastic diseases as the unique tumor principle[3]) emerged to embrace the ubiquitous phenomenon of heterogeneity of disease etiology and pathogenesis. As the exposome is a common concept of epidemiology, personalized medicine is intertwined with molecular pathological epidemiology (MPE). MPE research is capable of identifying potential biomarkers for personalized precision medicine.[4]

Historically, the pharmaceutical industry has developed medications based on empiric observations and more recently, known disease mechanisms.[citation needed] For example, antibiotics were based on the observation that microbes produce substances that inhibit other species. Agents that lower blood pressure have typically been designed to act on certain pathways involved in hypertension (such as renal salt and water absorption, vascular contractility, and cardiac output). Medications for high cholesterol target the absorption, metabolism, and generation of cholesterol. Treatments for diabetes are aimed at improving insulin release from the pancreas and sensitivity of the muscle and fat tissues to insulin action. Thus, medications are developed based on mechanisms of disease that have been extensively studied over the past century. It is hoped that recent advancements in the genetic etiologies of common diseases will improve pharmaceutical drug development.[1]

Contributory Fields, Discoveries, and Technologies[edit]

Since the late 1990s, the advent of research using biobanks has brought advances in molecular biology, proteomics, metabolomic analysis, genetic testing, and molecular medicine. Another significant development has been the notion of companion diagnostics, whereby molecular assays that measure levels of proteins, genes, or specific mutations are used to provide a specific therapy for an individual's condition - by stratifying disease status, selecting the proper medication, and tailoring dosages to that patient's specific needs. Additionally, such methods might be used to assess a patient's risk factor for a number of conditions and tailor individual preventative treatments.

Pharmacogenetics (also termed pharmacogenomics) is the field of study that examines the impact of genetic variation and responses to therapeutic interventions by biomarker (medicine).[5] This approach is aimed at tailoring drug therapy at a dosage that is most appropriate for an individual patient, with the potential benefits of increasing the efficacy and safety of medications.[6] Other benefits include reduced time, cost, and failure rates of clinical trials in the production of new drugs by using precise biomarkers.[7] Gene-centered research may also speed the development of novel therapeutics.[8]

The field of proteomics, or the comprehensive analysis and characterization of all of the proteins and protein isoforms encoded by the human genome, may eventually have a significant impact on medicine. This is because while the DNA genome[9] is the information archive, it is the proteins that do the work of the cell: the functional aspects of the cell are controlled by and through proteins, not genes.

It has also been demonstrated that pre-dose metabolic profiles from urine can be used to predict drug metabolism.[10][11] Pharmacometabolomics refers to the direct measurement of metabolites in an individual’s bodily fluids, in order to predict or evaluate the metabolism of pharmaceutical compounds.



Genotyping is the process of determining differences in the genetic make-up (genotype) of an individual by examining the individual's DNA sequence using biological assays. Example of this in PM include:

  • Genotyping for SNPs in genes involved in the action and metabolism of warfarin (Coumadin). This medication is used clinically as an anticoagulant but requires periodic monitoring and is associated with adverse side affects. Recently, genetic variants in the gene encoding Cytochrome P450 enzyme CYP2C9, which metabolizes warfarin,[12] and the Vitamin K epoxide reductase gene (VKORC1), a target of coumarins,[13] have led to commercially-available testing that enables more accurate dosing based on algorithms that take into account the age, gender, weight, and genotype of an individual.
  • Genotyping variants in genes encoding Cytochrome P450 enzymes (CYP2D6, CYP2C19, and CYP2C9), which metabolize neuroleptic medications, to improve drug response and reduce side-effects.[14]

Pharmaceutical compounding and custom-produced therapeutics[edit]

In addition to tailored administration of mass-produced therapeutics, PM also includes the tailored production of drugs or other medical products. This includes technologies for producing, as prescribed, customized pharmaceutical drug products like pills or polypills containing individualized dose levels for one or more drug substances.[15] Such technologies essentially facilitate the traditional practice of pharmacy compounding, i.e. preparing medicines individually for specific patients to reflect particular needs regarding strength and/or formulation. And when multi-drug polypills are made via compounding, it can serve as an alternative to using mass-produced fixed dose combination drug products.[16][17] Such compounding technologies may be used alone or in response to PM-informed decisions on the diagnostic side.

Condition-specific examples[edit]

Cancer management[edit]

Oncology is a field of medicine with a long history of classifying tumor stages and subtypes based on anatomic and pathologic findings. This approach includes histological examination of tumor specimens from individual patients (such as HER2/NEU in breast cancer) to look for markers associated with prognosis and likely treatment responses. Thus, "personalized medicine" was in practice long before the term was coined. New molecular testing methods have enabled an extension of this approach to include testing for global gene, protein, and protein pathway activation expression profiles and/or somatic mutations in cancer cells from patients in order to better define the prognosis in these patients and to suggest treatment options that are most likely to succeed.[18][19]

Examples of personalized cancer management include:

  • Companion diagnostics for targeted therapies.
    • Trastuzumab (trade names Herclon, Herceptin) is a monoclonal antibody drug that interferes with the HER2/neu receptor. Its main use is to treat certain breast cancers. This drug is only used if a patient's cancer is tested for overexpression of the HER2/neu receptor. Two tissue-typing tests are used to screen patients for possible benefit from Herceptin treatment. The tissue tests are immunohistochemistry(IHC) and Fluorescence In Situ Hybridization(FISH)[20] Only Her2+ patients will be treated with Herceptin therapy (trastuzumab)[21]
    • Tyrosine kinase inhibitors such as imatinib (marketed as Gleevec) have been developed to treat chronic myeloid leukemia (CML), in which the BCR-ABL fusion gene (the product of a reciprocal translocation between chromosome 9 and chromosome 22) is present in >95% of cases and produces hyperactivated abl-driven protein signaling. These medications specifically inhibit the Ableson tyrosine kinase (ABL) protein and are thus a prime example of "rational drug design" based on knowledge of disease pathophysiology.[22]
  • Testing for disease-causing mutations in the BRCA1 and BRCA2 genes, which are implicated in hereditary breast–ovarian cancer syndromes. Discovery of a disease-causing mutation in a family can inform "at-risk" individuals as to whether they are at higher risk for cancer and may prompt individualized prophylactic therapy including mastectomy and removal of the ovaries. This testing involves complicated personal decisions and is undertaken in the context of detailed genetic counseling. More detailed molecular stratification of breast tumors may pave the way for future tailored treatments.[23] These tests are part of the emerging field of cancer genetics, which is a specialized field of medical genetics concerned with hereditary cancer risk.

Psychiatry and psychological therapy[edit]

Efforts are underway to apply the tools of personalized medicine to psychiatry and psychological therapy; these technologies are still under development as of 2013.

In 2012 Professor Thalia Eley and her research team coined the term "therapygenetics" refers to a branch of psychiatric genetic research looking at the relationship between specific genetic variants and differences in the level of success of psychological therapy.[24][25] The field is parallel to pharmacogenetics, which explores the association between specific genetic variants and the efficacy of drug treatments. Therapygenetics work also relates to the differential susceptibility hypothesis [26] which proposes that individuals have a genetic predisposition to respond to a greater or lesser extent to their environment, be it positive or negative.

See also[edit]


  1. ^ a b c d Ginsburg, G. S.; Staples, J.; Abernethy, A. P. (2011). "Academic Medical Centers: Ripe for Rapid-Learning Personalized Health Care" (Free PDF download). Science Translational Medicine 3 (101): 101cm27. doi:10.1126/scitranslmed.3002386. PMID 21937754. 
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  4. ^ Ogino S, Lochhead P, Giovannucci E, Meyerhardt JA, Fuchs CS, Chan AT. Discovery of colorectal cancer PIK3CA mutation as potential predictive biomarker: power and promise of molecular pathological epidemiology. Oncogene advance online publication 24 June 2013; doi: 10.1038/onc.2013.244
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  6. ^ Ozdemir, Vural; Williams-Jones, Bryn; Glatt, Stephen J; Tsuang, Ming T; Lohr, James B; Reist, Christopher (August 2006). "Shifting emphasis from pharmacogenomics to theranostics". Nature Biotechnology 24 (8): 942–946. doi:10.1038/nbt0806-942. PMID 16900136. Retrieved 30 March 2013. 
  7. ^ Galas, D. J., & Hood, L. (2009). "Systems Biology and Emerging Technologies Will Catalyze the Transition from Reactive Medicine to Predictive, Personalized, Preventive and Participatory (P4) Medicine". Interdisciplinary Bio Central 1 (2): 1–4. doi:10.4051/ibc.2009.2.0006. 
  8. ^ Shastry BS (2006). "Pharmacogenetics and the concept of individualized medicine". Pharmacogenomics J. 6 (1): 16–21. doi:10.1038/sj.tpj.6500338. PMID 16302022. 
  9. ^ Harmon, Katherine (2010-06-28). "Genome Sequencing for the Rest of Us". Scientific American. Retrieved 2010-08-13. 
  10. ^ Clayton TA, Lindon JC, Cloarec O, et al.; Lindon; Cloarec; Antti; Charuel; Hanton; Provost; Le Net; Baker; Walley; Everett; Nicholson (April 2006). "Pharmaco-metabonomic phenotyping and personalized drug treatment". Nature 440 (7087): 1073–7. Bibcode:2006Natur.440.1073A. doi:10.1038/nature04648. PMID 16625200. 
  11. ^ Clayton TA, Baker D, Lindon JC, Everett JR, Nicholson JK; Baker; Lindon; Everett; Nicholson (August 2009). "Pharmacometabonomic identification of a significant host-microbiome metabolic interaction affecting human drug metabolism". Proc. Natl. Acad. Sci. U.S.A. 106 (34): 14728–33. Bibcode:2009PNAS..10614728C. doi:10.1073/pnas.0904489106. PMC 2731842. PMID 19667173. 
  12. ^ Schwarz UI (November 2003). "Clinical relevance of genetic polymorphisms in the human CYP2C9 gene". Eur. J. Clin. Invest. 33. Suppl 2: 23–30. doi:10.1046/j.1365-2362.33.s2.6.x. PMID 14641553. 
  13. ^ Oldenburg J, Watzka M, Rost S, Müller CR (July 2007). "VKORC1: molecular target of coumarins". J. Thromb. Haemost. 5. Suppl 1: 1–6. doi:10.1111/j.1538-7836.2007.02549.x. PMID 17635701. 
  14. ^ Cichon S, Nöthen MM, Rietschel M, Propping P (2000). "Pharmacogenetics of schizophrenia". Am. J. Med. Genet. 97 (1): 98–106. doi:10.1002/(SICI)1096-8628(200021)97:1<98::AID-AJMG12>3.0.CO;2-W. PMID 10813809. 
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  17. ^ Sandler, N.; Määttänen, A.; Ihalainen, P.; Kronberg, L.; Meierjohann, A.; Viitala, T.; Peltonen, J. (2011). "Inkjet printing of drug substances and use of porous substrates-towards individualized dosing". Journal of Pharmaceutical Sciences 100 (8): 3386–3395. doi:10.1002/jps.22526. PMID 21360709
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  19. ^ van't Veer LJ, Bernards R; Bernards (April 2008). "Enabling personalized cancer medicine through analysis of gene-expression patterns". Nature 452 (7187): 564–70. Bibcode:2008Natur.452..564V. doi:10.1038/nature06915. PMID 18385730. 
  20. ^ Carney, Walter (2006). "HER2/neu Status is an Important Biomarker in Guiding Personalized HER2/neu Therapy". Connection 9: 25–27. 
  21. ^ Telli, M. L.; Hunt, S. A.; Carlson, R. W.; Guardino, A. E. (2007). "Trastuzumab-Related Cardiotoxicity: Calling Into Question the Concept of Reversibility". Journal of Clinical Oncology 25 (23): 3525–3533. doi:10.1200/JCO.2007.11.0106. ISSN 0732-183X. PMID 17687157. 
  22. ^ Saglio G, Morotti A, Mattioli G, et al. (December 2004). "Rational approaches to the design of therapeutics targeting molecular markers: the case of chronic myelogenous leukemia". Ann. N. Y. Acad. Sci. 1028 (1): 423–31. Bibcode:2004NYASA1028..423S. doi:10.1196/annals.1322.050. PMID 15650267. 
  23. ^ Gallagher, James (19 April 2012). "Breast cancer rules rewritten in 'landmark' study". BBC News. Retrieved 19 April 2012. 
  24. ^ Lester, KJ; Eley TC (2013). "Therapygenetics: Using genetic markers to predict response to psychological treatment for mood and anxiety disorders". Biology of mood & anxiety disorders 3 (1): 1–16. doi:10.1186/2045-5380-3-4. PMC 3575379. PMID 23388219. 
  25. ^ Beevers, CG; McGeary JE (2012). "Therapygenetics: moving towards personalized psychotherapy treatment". Trends in Cognitive Sciences 16 (1): 11–12. doi:10.1016/j.tics.2011.11.004. PMC 3253222. PMID 22104133. 
  26. ^ Belsky J, Jonassaint C, Pluess M, Stanton M, Brummett B, Williams R (August 2009). "Vulnerability genes or plasticity genes?". Mol. Psychiatry 14 (8): 746–54. doi:10.1038/mp.2009.44. PMC 2834322. PMID 19455150. 

Further reading[edit]

  • Daskalaki A, Wierling C, Herwig R (2009), Computational tools and resources for systems biology approaches in cancer.In Computational Biology - Issues and Applications in Oncology, Series: Applied Bioinformatics and Biostatistics in Cancer Research, Pham, Tuan (Ed.), Springer, New York Dordrecht Heidelberg London. 2009:227-242.
  • Acharya et al. (2008), Gene Expression Signatures, clinicopathological features, and individualized therapy in breast cancer, JAMA 299: 1574.
  • Sadee W, Dai Z. (2005), Pharmacogenetics/genomics and personalized medicine, Hum Mol Genet. 2005 October 15;14 Spec No. 2:R207-14.
  • Steven H. Y. Wong (2006), Pharmacogenomics and Proteomics: Enabling the Practice of Personalized Medicine, American Association for Clinical Chemistry, ISBN 1-59425-046-4
  • Qing Yan (2008), Pharmacogenomics in Drug Discovery and Development, Humana Press, 2008, ISBN 1-58829-887-6.
  • Willard, H.W., and Ginsburg, G.S., (eds), (2009), Genomic and Personalized Medicine, Academic Press, 2009, ISBN 0-12-369420-5.
  • Haile, Lisa A. (2008), Making Personalized Medicine a Reality, Genetic Engineering & Biotechnology News Vol. 28, No. 1.
  • Hornberger J, Habraken H, Bloch DA. Minimum data needed on patient preferences for accurate, efficient medical decision making. Medical Care 1995; 33:297-310.
  • Lyman GH, Cosler LE, Kuderer NM, Hornberger J. Impact of a 21-gene RT-PCR assay on treatment decisions in early-stage breast cancer: an economic analysis based on prognostic and predictive validation studies. Cancer 2007; 109(6):1011-8.
  • Hornberger J, Cosler L and Lyman G. Economic analysis of targeting chemotherapy using a 21-gene RT-PCR assay in lymph-node–negative, estrogen-receptor–positive, early-stage breast cancer. Am J Managed Care 2005; 11:313-24.
  • A.Daskalaki & A.Lazakidou (2011). Quality Assurance in Healthcare Service Delivery, Nursing and Personalized Medicine: Technologies and Processes. IGI Global. ISBN 978-1-61350-120-7
  • Picard FJ, Bergeron MG., Rapid molecular theranostics in infectious diseases, Drug Discov Today. 2002 Nov 1;7(21):1092-101.
  • Hooper JW., The genetic map to theranostics, MLO Med Lab Obs. 2006 Jun;38(6):22-3, 25.

External links[edit]

  • CancerDriver : a free and open database to promote personalized medicine in oncology.