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 Table of Contents  
REVIEW ARTICLE
Year : 2015  |  Volume : 27  |  Issue : 1  |  Page : 76-80

Personalized medicine: A step forward in dental treatment


Department of Oral Medicine and Radiology, PDM Dental College and Research Institute, Haryana, India

Date of Submission28-Oct-2014
Date of Acceptance13-Jul-2015
Date of Web Publication12-Oct-2015

Correspondence Address:
Surbhi
PDM Dental College and Research Institute, Sarai Aurangaband, Bahadurgarh, Jhajjar, Haryana
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0972-1363.167089

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   Abstract 

The study of variations of DNA and RNA characteristics as related to drug response is known as pharmacogenomics. The application of pharmacogenomics to the clinical management of an individual is referred to as "personalized medicine." Personalized medicine aims to individualize care based on a person's unique genetic profile by using advanced molecular tools like DNA profiling, gene mapping, receptor gene amplification test, fluorescence in situ hybridization (FISH), microarray test, Hercep Test, AmpliChip CYP450 Test, etc. This is relatively a new field that combines genomics (the study of genes and their functions) and pharmacology (the science of drugs) to develop effective, safe medications and doses that will be tailored to a person's genetic makeup. Now personalized medicine has a wide range of applications such as management of cancer, cardiovascular disorders, depression, bipolar disorders, attention deficit disorders, HIV, tuberculosis, asthma, diabetes, and also in the management of pain. This is the first article focusing on its mechanism, overview of the developments, benefits, challenges, and its applications, particularly in dentistry.

Keywords: Genetic mapping, personalized medicine, pharmacogenetics, pharmacogenomics


How to cite this article:
Surbhi, Kumar A, Nagpal A, Vohra P. Personalized medicine: A step forward in dental treatment. J Indian Acad Oral Med Radiol 2015;27:76-80

How to cite this URL:
Surbhi, Kumar A, Nagpal A, Vohra P. Personalized medicine: A step forward in dental treatment. J Indian Acad Oral Med Radiol [serial online] 2015 [cited 2020 May 25];27:76-80. Available from: http://www.jiaomr.in/text.asp?2015/27/1/76/167089


   Introduction Top


It has long been known that patients treated with various drugs have different kinds of response and susceptibility to drug toxicity. The variations in the body's response to drug treatment may be due to several factors such as illness, differences in pharmacokinetics and pharmacodynamics of drugs, environmental factors, and genetic factors. [1] The National Cancer Institute defined personalized medicine (PM) as "a form of medicine that uses information about a person's genes, proteins, and environment to prevent, diagnose, and treat the disease." [2] At present, PM is mainly applied in the following areas: [3]

  • Prediction
  • Diagnostics
  • Therapeutics
  • Drug development



   Mechanism of PM Top


The traditional standard approaches to drug development and clinical therapy, such as "trail and error," "one drug fits all," and "one dose fits all," are highly limited, contributing to 25-50% of drug toxicity and treatment failure [4] [Figure 1]. Recognition of inter-individual differences in drug response is an essential step toward optimizing therapy. Pharmacogenomics, on the other hand, takes advantage of genomic techniques such as DNA sequencing, gene mapping, and bioinformatics to allow researchers to identify the actual genetic basis of inter-individual and inter-racial variation in drug efficacy, metabolism, and transport [5] [Figure 2].
Figure 1: Medicine of present: One fi ts all

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Figure 2: Medicine of future: Personalized medicine

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Genetic polymorphisms and mutations in drug metabolizing enzymes, transporters, receptors, and other drug targets (e.g., toxicity targets) are linked to inter-individual differences in the efficacy and toxicity of many medications, as well as the risk of genetic diseases. [6]

Single-nucleotide polymorphisms

Single-nucleotide polymorphisms (SNPs) are the most frequently found DNA sequence variations in the human genome. It is believed that SNPs may contribute significantly to genetic risk for common diseases. It is estimated that the average nucleotide diversity is 1 difference/1200 base pairs. Approximately 1 million SNPs are likely to occur in human genes. Single-nucleotide polymorphisms found in the coding and regulatory regions of genes are likely to be the most relevant variants. Efforts to identify all SNPs and their relevance to disease (cancer) susceptibility and treatment outcome are continuous, and may take several more years. [7]

Drug-metabolizing enzymes

There are more than 30 families of drug-metabolizing enzymes in humans, and essentially all have genetic variants, many of which translate into functional changes in the proteins encoded. [8] The cytochrome P450 monooxygenase system of enzymes is responsible for a major portion of drug metabolism in humans. This large family of genes has been intensely studied, and among the numerous P450 subtypes, CYP2D6, 3A4/3A5, 1A2, 2E1, 2C9, and 2C19 particularly play critical roles in genetically determined responses to a broad spectrum of drugs [5] [Table 1].
Table 1: Examples of inherited or acquired variations in enzymes and receptors that affect drug response[5]

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Drug transporters

Transport proteins have an important role in regulating the absorption, distribution, and excretion of many medications. For example, genetic variability in drug transporters plays a role in the resistance of malignant cells to anticancer agents. For instance, polymorphism in the ABC-binding cassette (ABC) gene may affect the function and expression of proteins. This may cause certain drug-induced side effects and uncertainty in treatment efficacy [9] [Table 1].


   Methods Used Top


Pharmacogenomic methods are based on recent technological advances that made parallel analysis of genetic information of humans with mathematical and statistical apparatus possible, which enables the overview and analysis of the resulting multidimensional biological data. [9] The common elements of this approach to nucleic acid analysis are an immobilized or tethered nucleic acid (DNA or RNA) species that is hybridized with a second, solution-phase DNA or RNA species that is generally labeled with a detectable molecule such as a fluorescent dye. The sequence of the unknown "target" nucleic acid is determined by decoding its complementarities with the nucleic acid "probe" of known sequence. Whether the probe or target nucleic acid is immobilized varies among the different array methods, but most commonly, the probe is tethered to a surface and the target to be analyzed is in solution. [5]

Lab card or lab-on-a-chip devices are becoming increasingly important in genomic analysis. Microcapillary electrophoresis separation devices pioneered less than 10 years ago by Harrison, Ramsay, Mathies, and others have virtually replaced traditional gel electrophoresis. Lab cards with complex networks of microcapillary channels finer than human hair have now been demonstrated to be useful not only for molecular separations but also to carry out nanoscale biochemical reactions. [5]

Polymerase chain reactions, sequencing reactions, primer extension reactions, and nuclease cleavage reactions carried out in these devices realize an order of magnitude improvement in throughput and economy over microtiter plate-based biochemistry. Genomic techniques are making it possible not only to identify tangible new gene targets for drug discovery efforts, but also to find associations between specific genetic markers and drug response in a patient population. [5]


   Applications of PM Top


Although the promise of pharmacogenomics is enormous, it is likely to have the greatest initial benefit for patients in developed countries owing to expense, availability of technology, and the focus of initial research. [10]

Dental implications

The mouth is a portal of entry as well as a mirror which reflects a wealth of information that can be derived from oral fluid and tissues. The recent progress made in the human and microbial genomes provides unprecedented opportunities to not only understand the molecular basis of oral diseases but also design and fabricate new generations of diagnostics, therapeutics, and biomaterials [1] [Table 2].
Table 2: Main current clinical implications[1]

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   Benefits of PM Top


Improving patient safety

Pharmacogenetic testing may help identify patients who are likely to experience dangerous reactions to drugs, enabling doctors to monitor them closely and possibly adjust the dosing of the drug or choose another treatment, thereby improving patient safety and potentially saving lives. [7]

Improving health care costs and efficiency

The time and resources that doctors and patients spend finding appropriate medications and doses through "trial and error" are likely to decrease as pharmacogenetic tests are developed. [7]

More accurate methods of determining dosages

Instead of dosages being based on body weight and age, they would be based on an individual's genetics. This would decrease the likelihood of an overdose. [7]


   Barriers of the Field Top


Despite significant progress made in pharmacogenomics research, relatively little information has been effectively translated into clinical practice. This is the result of several issues, which are discussed here. [11]

Interpretation of pharmacogenomic studies

The complexity of genetic interactions, the multigenic origins of disease, and the influence of the environment often will make it difficult to apply pharmacogenetics to the clinic. Thus, an overarching challenge for pharmacogenomics in the future will be to devise effective experimental designs and data analysis strategies for the simultaneous investigation of multiple contributory genetic factors. [11]

Regulatory issues

With the evolution of genotyping technologies, the conduct of genome-wide association studies during clinical trials is becoming more feasible. Widespread use could result in market segregation and decreased revenue due to exclusion of patient subpopulations, as well as the potential for additional regulatory impositions. If a drug is developed with the knowledge that its efficacy or safety is correlated with a specific set of genetic markers, then use of the drug would ultimately need to be linked to a diagnostic test for that genetic profile. Therefore, establishing regulatory guidelines has been viewed as a key in bringing pharmacogenomics-based drugs to the market. With this in mind, integration of pharmacogenomics into drug development is being facilitated through US Food and Drug Administration (US FDA) initiatives. [11]

Costs of testing

Ideally, the introduction of pharmacogenomic tests in the clinical environment should include cost-effectiveness studies which are not available at present. Drugs are subject to a sophisticated scientific process for approval, including randomized clinical trials; but for diagnostic tests, randomized clinical trials may not be indicated at all or may be difficult. Therefore, the pharmacogenetic companies are faced with smaller benefits and more risks than the much more powerful pharmaceutical companies and, as a rule, lack the resources of the big drug companies, which is again a challenge for the upcoming field. [12]

Education

Effective integration of pharmacogenomic information into medical practice and patient care will require a significant effort to educate health care professionals. The majority of undergraduate programs in medicine and pharmacy currently have only minimal content in pharmacogenomics. Nevertheless, expansion of current undergraduate, professional, and continuing education programs will be required. As ethical issues and fear of genetic discrimination continue to arise in the general population, it is also crucial to inform and educate the public at the same time. [11]


   Conclusion Top


Although pharmacogenomics continues to improve understanding of drug response, progress is gradual, with clinical implementation lagging far behind. Several obstacles need to be overcome for successful application of pharmacogenomics to drug therapy. To summarize, pharmacogenomics serves as an increasingly powerful tool in understanding inter-individual variability in drug response and toxicity. Yet, decisive advances in drug therapy require an integrative systems approach, using medical informatics for optimizing PM.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
   References Top

1.
Freires IA. Pharmacogenomics and dental practice: Clinical implications and current researches. Odontol Clín-Cientifica 2012;11:97-101.  Back to cited text no. 1
    
2.
Margaret A. Paving the Way for Personalized Medicine: FDA's Role in a New Era of Medical Product Development. Available from: http://www.fda.gov/downloads/.../personalized medicine/ucm372421.pdf. [Last accessed on 2014 Feb 14].  Back to cited text no. 2
    
3.
Papassotiropoulos A. The Potential and Limits of Personalized Medicine: Position Paper Issued by the Swiss Academy of Medical Sciences. Available from: http://www.samw.ch/dms/en/Publications/.../e_ PersMedizin_PosPapier.pdf. [Last accessed on 2014 Feb 24].  Back to cited text no. 3
    
4.
Xie HG, Frueh FW. Pharmacogenomics steps toward personalized medicine. Per Med 2005;2:325-37.  Back to cited text no. 4
    
5.
Mancinelli L, Cronin M, Sadée W. Pharmacogenomics: The promise of personalized medicine. AAPS Pharm Sci 2000;2:E4.  Back to cited text no. 5
    
6.
Ishikawa T, Hayashizaki Y. Recent advances in pharmacogenomic technology for personalized medicine. In: Paxton J, editor. Topics on drug metabolism. Rijeka, Croatia: InTech; 2012. p. 281-94.  Back to cited text no. 6
    
7.
Toomula N, Hima Bindu K, Sathish Kumar D, Arun Kumar R. Pharmacogenomics- Personalized treatment of cancer, diabetes and cardiovascular diseases. J Pharmacogenomics Pharmacoproteomics 2011;2:107.  Back to cited text no. 7
    
8.
Evans WE, McLeod HL. Pharmacogenomics - drug disposition, drug targets, and side effects. New Engl J Med 2003;348:538-49.  Back to cited text no. 8
    
9.
Shashtry BS. Pharmacogenetics and the concept of individualized medicine. Pharmacogenomics J 2006;6:16-21.  Back to cited text no. 9
    
10.
McLeod HL, Evans WE. Pharmacogenomics: Unlocking the human genome for better drug therapy. Annu Rev Pharmacol Toxicol 2001;41:101-21.  Back to cited text no. 10
    
11.
Piquette-Miller M, Grant DM. The art and science of personalized medicine. Clin Pharmacol Ther 2007;81:311-5.  Back to cited text no. 11
    
12.
de Leon J. Pharmacogenomics: The promise of personalized medicine for CNS disorders. Neuropsychopharmacology 2009;34:159-72.  Back to cited text no. 12
    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2]



 

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