Precision Medicine: A New Paradigm in Therapeutics

Neha Akhoon

Abstract


A key goal of clinical care is to treat patients as individuals and to approach therapeutics in such a way that it has optimal efficacy and minimal toxicity. With swift technological advances, such as genomic sequencing and molecular targeted drug exploitation, the concept of precision medicine has been robustly promoted in recent years. Precision medicine endeavors to demarcate diseases using multiple data sources from genomics to digital health metrics in order to facilitate an individualized yet “evidence‑based” decision regarding diagnostic and therapeutic approaches. In this way, therapeutics can be centered toward patients based on their molecular presentation rather than grouping them into broad categories with a “one size fits all” approach. This review article is aimed to provide a broad overview of the advent and emergence of precision medicine in view of its current implications.

Keywords


Precision medicine; preventive medicine; therapeutics

Full Text:

PDF

References


Stone A. Precision medicine: Health care tailored to you. The

White House Blog; 2016.

Levy G. Pharmacologic target-mediated drug disposition. Clin

Pharmacol Ther 1994;56:248‑52.

Sackett DL, Rosenberg WM, Gray JA, Haynes RB, Richardson

WS. Evidence based medicine: What it is and what it isn’t. BMJ

;312:71‑2.

Evidence‑Based Medicine Working Group. Evidence‑based

medicine. A new approach to teaching the practice of medicine.

JAMA 1992;268:2420‑5.

Chow N, Gallo L, Busse J. Evidence‑based medicine and

precision medicine: Complementary approaches to clinical

decision‑making. Precis Clin Med 2018;1:60‑4.

Bensing J. Bridging the gap: The separate worlds of

evidence‑based medicine and patient‑centered medicine. Patient

Educ Couns 2000;39:17‑25.

Groopman J. How doctors think. Houghton Mifflin Harcourt;

Abrams J, Conley B, Mooney M, Zwiebel J, Chen A, Welch JJ,

et al. National cancer institute’s precision medicine initiatives

for the new national clinical trials network. Am Soc Clin Oncol

Educ Book 2014;34:71‑6.

Biankin AV, Piantadosi S, Hollingsworth SJ. Patient‑centric

trials for therapeutic development in precision oncology. Nature

;526:361‑70.

Redig AJ, Jänne PA. Basket trials and the evolution of clinical

trial design in an era of genomic medicine. J Clin Oncol

;33:975‑7.

Peck R. Precision medicine is not just genomics: The right dose

for every patient. Ann Rev Pharmacol Toxicol 2018;58:105‑22.

Kola I, Bell J. A call to reform the taxonomy of human disease.

Nat Rev Drug Discov 2011;10:641‑2.

National Research Council. Toward Precision Medicine: Building

a Knowledge Network for Biomedical Research and a New

Taxonomy of Disease. National Academies Press; 2011.

Chan AC, Behrens TW. Personalizing medicine for autoimmune

and inflammatory diseases. Nat Immunol 2013;14:106‑9.

Hyman DM, Puzanov I, Subbiah V, Faris JE, Chau I, Blay JY,

et al. Vemurafenib in multiple nonmelanoma cancers with BRAF

V600 mutations. N Engl J Med 2015;373:726‑36.

Munnink TO, Henstra MJ, Segerink LI, Movig KL,

Brummelhuis-Visser P. Therapeutic drug monitoring of

monoclonal antibodies in inflammatory and malignant disease:

Translating TNF-α experience to oncology. Clin Pharmacol Ther

;99:419‑31.

Dugger SA, Platt A, Goldstein DB. Drug development in the era

of precision medicine. Nat Rev Drug Discov 2018;17:183‑96.

Stegmeier F, Warmuth M, Sellers WR, Dorsch M. Targeted

cancer therapies in the twenty-first century: Lessons from

imatinib. Clin Pharmacol Ther 2010;87:543‑52.

Slamon DJ, Leyland‑Jones B, Shak S, Fuchs H, Paton V,

Bajamonde A, et al. Use of chemotherapy plus a monoclonal

antibody against HER2 for metastatic breast cancer that

overexpresses HER2. N Engl J Med 2001;344:783‑92.

Chae YK, Pan A, Davis AA, Raparia K, Mohindra NA,

Matsangou M, et al. Biomarkers for PD‑1/PD‑L1 blockade

therapy in non–small‑cell lung cancer: Is PD‑L1 expression

a good marker for patient selection?. Clin Lung Cancer

;17:350‑61.

Abdel‑Rahman O. Correlation between PD‑L1

expression and outcome of NSCLC patients treated with

anti‑PD‑1/PD‑L1 agents: A meta‑analysis. Crit Rev Oncol

Hematol 2016;101:75‑85.

National Comprehensive Cancer Network. National

Comprehensive Cancer Network Guidelines in Oncology.

Non‑Small Cell Lung Cancer Version 7. 2015.

Slavin RG, Ferioli C, Tannenbaum SJ, Martin C, Blogg M,

Lowe PJ. Asthma symptom re‑emergence after omalizumab

withdrawal correlates well with increasing IgE and decreasing

pharmacokinetic concentrations. J Allergy Clin Immunol

;123:107‑13.

Han K, Jin J, Maia M, Lowe J, Sersch MA, Allison DE. Lower

exposure and faster clearance of bevacizumab in gastric cancer

and the impact of patient variables: Analysis of individual data

from AVAGAST phase III trial. AAPS J 2014;16:1056‑63.

Stolar MW. Defining and achieving treatment success in patients

with type 2 diabetes mellitus. Mayo Clin Proc 2010;85:S50‑9.

Gloyn AL, Pearson ER, Antcliff JF, Proks P, Bruining GJ,

Slingerland AS, et al. Activating mutations in the gene encoding

the ATP‑sensitive potassium‑channel subunit Kir6. 2 and

permanent neonatal diabetes. N Engl J Med 2004;350:1838‑49.

Pearson ER, Flechtner I, Njølstad PR, Malecki MT, Flanagan SE,

Larkin B, et al. Switching from insulin to oral sulfonylureas in

patients with diabetes due to Kir6. 2 mutations. N Engl J Med

;355:467‑77.

Babenko AP, Polak M, Cavé H, Busiah K, Czernichow P,

Scharfmann R, et al. Activating mutations in the ABCC8 gene in

neonatal diabetes mellitus. N Engl J Med 2006;355:456‑66.

Rafiq M, Flanagan SE, Patch AM, Shields BM, Ellard S,

Hattersley AT, Neonatal Diabetes International Collaborative

Group. Effective treatment with oral sulfonylureas in patients

with diabetes due to sulfonylurea receptor 1 (SUR1) mutations.

Diabetes Care 2008;31:204‑9.

Magen D, Sprecher EL, Zelikovic I, Skorecki K. A novel

missense mutation in SLC5A2 encoding SGLT2 underlies

autosomal‑recessive renal glucosuria and aminoaciduria. Kidney

Int 2005;67:34‑41.

Stolar MW. Defining and achieving treatment success in patients

with type 2 diabetes mellitus. In Mayo Clin Proc 2010:85, No.

, pp. S50‑S59). Elsevier.

Mulvihill EE, Drucker DJ. Pharmacology, physiology, and

mechanisms of action of dipeptidyl peptidase‑4 inhibitors.

Endocr Rev 2014;35:992‑1019.

Scott RA, Freitag DF, Li L, Chu AY, Surendran P, Young R, et al.

A genomic approach to therapeutic target validation identifies a

glucose‑lowering GLP1R variant protective for coronary heart

disease. Sci Transl Med 2016;8:341ra76.

Dadu RT, Ballantyne CM. Lipid lowering with PCSK9 inhibitors.

Nat Rev Cardiol 2014;11:563‑75.

Dewey FE, Gusarova V, O’Dushlaine C, Gottesman O, Trejos J,

Hunt C, et al. Inactivating variants in ANGPTL4 and risk of

coronary artery disease. N Engl J Med 2016;374:1123‑33.

Phillips KA, Veenstra DL, Oren E, Lee JK, Sadee W. Potential

role of pharmacogenomics in reducing adverse drug reactions: A

systematic review. JAMA 2001;286:2270‑9.

BlueCross BlueShield Association. Special report: Genotyping

for cytochrome P450 polymorphisms to determine drugmetabolizer status. Chicago: BlueCross BlueShield Association

(BCBS). TEC Assessment 2004;19.

Stekler J, Maenza J, Stevens C, Holte S, Malhotra U,

McElrath MJ, et al. Abacavir hypersensitivity reaction in primary

HIV infection. Aids 2006;20:1269‑74.

Man CB, Kwan P, Baum L, Yu E, Lau KM, Cheng AS, et al.

Association between HLA-B* 1502 allele and antiepileptic druginduced cutaneous reactions in Han Chinese. Epilepsia. 2007

May;48(5):1015-8.

SEARCH Collaborative Group. SLCO1B1 variants and

statin‑induced myopathy—a genomewide study. N Engl J Med

;359:789‑99.

Hamberg AK, Dahl ML, Barban M, Scordo MG, Wadelius M,

Pengo V, et al. A PK–PD model for predicting the impact of

age, CYP2C9, and VKORC1 genotype on individualization of

warfarin therapy. Clin Pharmacol Ther 2007;81:529‑38.

International Warfarin Pharmacogenetics Consortium. Estimation

of the warfarin dose with clinical and pharmacogenetic data. N

Engl J Med 2009;360:753‑64.

Avery PJ, Jorgensen A, Hamberg AK, Wadelius M,

Pirmohamed M, Kamali F. A proposal for an individualized

pharmacogenetics-based warfarin initiation dose regimen for

patients commencing anticoagulation therapy. Clin Pharmacol

Ther 2011;90:701‑6.

Raue F, Frank‑Raue K, Grauer A. Multiple endocrine neoplasia

type 2: Clinical features and screening. Endocrinol Metab Clin

North Am 1994;23:137‑56.

Chae YK, Pan A, Davis AA, Raparia K, Mohindra NA, Matsangou

M, et al. Biomarkers for PD‑1/PD‑L1 blockade therapy in non–

small‑cell lung cancer: Is PD‑L1 expression a good marker for

patient selection?. Clin Lung Cancer 2016;17:350‑61.

Azizi F. Precision medicine for endocrinology. Int J Endocrinol

Metab 2016;14:e40283.

Collins FS, Varmus H. A new initiative on precision medicine. N

Engl J Med 2015;372:793‑5.

Cardoso F, Van’t Veer LJ, Bogaerts J, Slaets L, Viale G,

Delaloge S, et al. 70‑gene signature as an aid to treatment decisions

in early‑stage breast cancer. N Engl J Med 2016;375:717‑29.

Mager DE, Jusko WJ. General pharmacokinetic model for drugs

exhibiting target‑mediated drug disposition. J Pharmacokinetics

Pharmacodyn 2001;28:507‑32.

Gameiro GR, Sinkunas V, Liguori GR, Auler‑Júnior JO. Precision

medicine: Changing the way we think about healthcare. Clinics

(Sao Paulo) 2018;73:e723.

Meijers‑Heijboer H, van Geel B, van Putten WL,

Henzen‑Logmans SC, Seynaeve C, Menke‑Pluymers MB,

et al. Breast cancer after prophylactic bilateral mastectomy

in women with a BRCA1 or BRCA2 mutation. N Engl J Med

;345:159‑64.

Soda M, Choi YL, Enomoto M, Takada S, Yamashita Y,

Ishikawa S, et al. Identification of the transforming EML4–ALK

fusion gene in non‑small‑cell lung cancer. Nature 2007;448:561‑6.

Topol EJ. Individualized medicine from prewomb to tomb. Cell

;157:241‑53.

Ramaswami R, Bayer R, Galea S. Precision medicine

from a public health perspective. Ann Rev Public Health

;39:153‑68.

Ginsburg GS, Phillips KA. Precision medicine: From science to

value. Health Aff (Millwood) 2018;37:694‑701.