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    Personalized medicine: Right drug, right patient, right time

    The premise is to use a patient’s own genetic information to guide decisions for prevention, diagnosis, and treatment of disease and other health conditions.

     

    PAIN MANAGEMENT

    Atypical cytochrome P450 2D6 (CYP2D6) pharmacogenetics is both indicative of a poor pain response and associated with several postoperative deaths following the use of codeine for pain management. Poor metabolizers of CYP2D6 may never achieve pain control and rapid metabolizers may experience severe toxic effects. Although some hospitals have simply removed codeine from their formularies, St. Jude Children’s Research Hospital, Memphis, Tennessee, and others have developed pharmacogenetic testing programs for its safe use through widespread testing.14-16

    PEDIATRIC CANCER

    In addition to identification of the TMPT gene mentioned previously for the use of 6-mercaptopurine, associations with certain genes have been linked to risks for ototoxicity from cisplatins and cardiotoxicity from anthracyclines.17 Similarly, there is hope that genetic testing may be able to identify patients at increased risk of adverse effects from chemotherapy such as neuropathy, neurocognitive problems, and several other adverse effects in pediatric cancer treatment.18,19

    Genetic subtypes also have been associated with outcomes and likely response to treatment. Some genetic subtype advances have identified patients likely to experience poor outcomes in acute lymphoblastic leukemia (ALL) therapy and in need of a different therapeutic approach.20,21 On the other hand, some genetic subtypes indicate that certain patients’ cancers are more likely to respond to particular drugs and are targets for therapy tailored to an individual patient.22 The development of targeted and novel therapies based on the genetics of pediatric cancer has lagged behind their identification, but a great deal of studies are ongoing.

    Conclusions

    Genomic analysis will continue to impact how pediatricians identify and treat disease. It will be important for pediatricians to increase their knowledge and skills in this quickly changing field to be able not only to implement competency in their own practice, but also to explain to patients and parents so they can fully understand.

    Next: Reimagining chemotherapy

    The pediatrician is also likely to be challenged because, as the field is advancing quickly, the literature has not often addressed areas that other aspects of medicine do not often address, such as the impact of developmental stages and how this might affect diagnosis or treatment.

    REFERENCES

    1. Yousif TI, Bizanti K, Elnazir B. Uses of personalized medicine in current pediatrics. Int J Clin Pediatr. 2016;5(1):1-5.

    2. Elborn JS. The impact of personalised therapies on respiratory medicine. Eur Respir Rev. 2013;22(127):72-74.

    3. Bloss CS, Schork NJ, Topol EJ. Effect of direct-to-consumer genomewide profiling to assess disease risk. N Engl J Med. 2011;364(6):524-534.

    4. Coote JH, Joyner MJ. Is precision medicine the route to a healthy world? Lancet. 2015;385(9978):1617.

    5. Vogenberg FR, Barash CI, Pursel M. Personalized medicine: part 3: challenges facing health care plans in implementing coverage policies for pharmacogenomics and genetic testing. P T. 2010;35(12):670-675.

    6. Basu K, Palmer CN, Tavendale R, Lipworth BJ, Mukhopadhyay S. Adrenergic beta(2)-receptor genotype predisposes to exacerbations in steroid-treated asthmatic patients taking frequent albuterol or salmeterol. J Allergy Clin Immunol. 2009;124(6):1188. e3-1194.e3.

    7. Tantisira KG, Lasky-Su J, Harada M, et al. Genomewide association between GLCCI1 and response to glucocorticoid therapy in asthma. N Engl J Med. 2011;365(13):1173-1183.

    8. Kieling C, Genro JP, Hutz MH, Rohde LA. A current update on ADHD pharmacogenomics. Pharmacogenomics. 2010;11(3):407-419.

    9. Shastry BS. Pharmacogenomics and its importance in pediatric medicine. J Pediatr Genet. 2012;1(2):79-84.

    10. Arns M, Olbrich S. Personalized medicine in ADHD and depression: use of pharmaco-EEG. In: Kumari V, Bob P, Boutros NN, eds. Electrophysiology and Psychophysiology in Psychiatry and Psychopharmacology. Vol 21. Cham, Switzerland: Springer International Publishing AG; 2014:345-370. Curr Top Behavioral Neurosci. 2014;21:345-370.

    11. Winner JG, Carhart JM, Altar CA, et al. Combinatorial pharmacogenomic guidance for psychiatric medications reduces overall pharmacy costs in a 1 year prospective evaluation. Curr Med Res Opin. 2015;31(9):1633-1643.

    12. Winner JG, Carhart JM, Altar CA, Allen JD, Dechairo BM. A prospective, randomized, double-blind study assessing the clinical impact of integrated pharmacogenomics testing for major depressive disorder. Discov Med. 2013;16(89):219-227.

    13. Hall-Flavin DK, Winner JG, Allen JD, et al. Utility of integrated pharmacogenomic testing to support the treatment of major depressive disorder in a psychiatric outpatient setting. Pharmacogenet Genomics. 2013;23(10):535-548.

    14. Rasmussen-Torvik LJ, Stallings SC, Gordon AS, et al. Design and anticipated outcomes of the eMERGEPGx project: a multicenter pilot for preemptive pharmacogenomics in electronic health record systems. Clin Pharmacol Ther. 2014;96(4):482-489.

    15. Hudak ML. Codeine pharmacogenetics as a proof of concept for pediatric precision medicine. Pediatrics. 2016;138(1):e20161359.

    16. Gammal RS, Crews KR, Haidar CE, et al. Pharmacogenetics for safe codeine use in sickle cell disease. Pediatrics. 2016;138(1):e20153479.

    17. Rieder MJ, Carleton B. Pharmacogenomics and adverse drug reactions in children. Front Genet. 2014;5:78.

    18. Mlakar V, Huezo-Diaz Curtis P, Satyanarayana Uppugunduri CR, Krajinovic M, Ansari M. Pharmacogenomics in pediatric oncology: review of gene-drug associations for clinical use. Int J Mol Sci. 2016;17(9):e1502.

    19. Kandula T, Park SB, Cohn RJ, Krishnan AV, Farrar MA. Pediatric chemotherapy induced peripheral neuropathy: a systematic review of current knowledge. Cancer Treat Rev. 2016;50:118-128.

    20. Den Boer ML, van Slegtenhorst M, De Menezes RX, et al. A subtype of childhood acute lymphoblastic leukaemia with poor treatment outcome: a genome-wide classification study. Lancet Oncol. 2009;10(2):125-134.

    21. Mullighan CG, Su X, Zhang J, et al; Children’s Oncology Group. Deletion of IKZF1 and prognosis in acute lymphoblastic leukemia. N Engl J Med. 2009;360(5):470-480.

    22. Roberts KG, Morin RD, Zhang J, et al. Genetic alterations activating kinase and cytokine receptor signaling in high-risk acute lymphoblastic leukemia. Cancer Cell. 2012;22(2):153-166.

    Pat F Bass III, MD, MS, MPH
    Dr Bass is Chief Medical Information officer and professor of Medicine and of Pediatrics, Louisiana State University Health Sciences ...

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