|Year : 2016 | Volume
| Issue : 2 | Page : 167-170
Tailor-made medicine: Is it practical?
Poornima Govindraju, Poornima Chandra, Balaji Pachipulusu, Mahesh Kumar Talkad Subbaiah
Department of Oral Medicine and Radiology, Rajarajeswari Dental College and Hospital, Bangalore, Karnataka, India
|Date of Submission||26-Aug-2015|
|Date of Acceptance||21-Nov-2016|
|Date of Web Publication||02-Dec-2016|
Department of Oral Medicine and Radiology, Rajarajeswari Dental College and Hospital, Bangalore - 560 074, Karnataka
Source of Support: None, Conflict of Interest: None
| Abstract|| |
It is a well-known fact that certain drugs work better for certain patients and some have adverse effects. This variation may be due to several factors such as illness, differences in pharmacokinetics and pharmacodynamics of drugs, environmental factors and genetic factors. Therefore, the analysis of the genes and genome will pave the way for effective diagnosis and management contributing to the development of personalized medicine. This treatment modality prescribes therapies specific to individual patients based on pharmacogenetic and pharmacogenomic information. This personalized medicine could be the key to developing patient-focused, cost-effective treatment from a dream to reality, however, some challenges exist.
Keywords: Genes, personalized medicine, pharmacogenetics, pharmacogenomics
|How to cite this article:|
Govindraju P, Chandra P, Pachipulusu B, Subbaiah MT. Tailor-made medicine: Is it practical?. J Indian Acad Oral Med Radiol 2016;28:167-70
|How to cite this URL:|
Govindraju P, Chandra P, Pachipulusu B, Subbaiah MT. Tailor-made medicine: Is it practical?. J Indian Acad Oral Med Radiol [serial online] 2016 [cited 2021 Apr 13];28:167-70. Available from: https://www.jiaomr.in/text.asp?2016/28/2/167/195132
| Introduction|| |
From perpetual times it is a well-known fact that heredity affects one's health, and all organisms including human beings have a genome which comprises all the biological information required to build and maintain a living example of that organism.  Segments of DNA that are found in all human cells are termed as genes. DNA is essentially a key part of our interactive chemical operating systems in the body instructing the body how to behave and interact at cellular level.  All the genetic material in the cells of a particular living organism is referred to as its genome. The human genome, thus, describes all the genetic material found in a human cell.  Genetics focuses or deals with single gene whereas genomics deals with interactions between all genes in the genome as well as the environmental factors. 
Except trauma, all diseases and disorders have a dominating genetic component. Human diseases may result either from single gene mutations, or more commonly, from complex and multiple gene-to-gene and gene-to-environment interactions.  The completion of the human genome project in 2003 was a major step which led to an array of several scientific discoveries;  sequencing and mapping of the human genome was one such impressive scientific breakthrough, which has brought new hope in the era of medicine. The introduction of computerized genotyping systems such as genechip and DNA microarray technologies revolutionized the genetics field.  The fact that the human genome has more than 20000 genes and millions of variations including the single nucleotide polymorphism emphasizes the importance of new technologies.  The rapid emergence and development of High Throughput Technologies made modern biological and medical researchers to shift from traditional hypothesis driven designs toward data driven studies. 
Applications of genomics and the knowledge of the sequence of human genome have inspired numerous -omics disciplines such as proteomics, epigenomics, transcriptomomicglycomics, and metabolic, mainly aiming us to understand the signaling pathways of the cell and thereby provide valuable insights into the pathogenesis of diseases leading to identification of new prognosticators, diagnostic markers and therapeutic targets. , Pharmacotherapy is one of the greatest clinical applications of genomic technology where the ultimate goal is to maximize response and minimize toxicity. ,
Physicians have known for centuries that certain medicines work better for certain patients and some have adverse effects. Individualized treatment was followed by Hippocrates by combining four humours blood, plegm, yellow bile and black bile were used to determine the best course of treatment for each patient. The variation in the response to treatment may be due to several factors such as illness, differences in pharmacokinetics and pharmacodynamics of drugs, environmental factors, and genetic factors. 
The uniqueness of an individual in the genetic makeup results in significant variability in expressing gene products such as enzymes involving metabolism of drugs, transporters of drugs, drug targets and their succeeding signal transduction molecules. It has been observed that the efficacy of drug therapy of many diseases was in the range of 20-80%, and 20% of the patients were poor responders. The limitation in the traditional approaches for the development of the drug and clinical therapies such as "trial and error" and "one drug fits all and one dose fits all" has lead to 20-50% of drug toxicities or treatment failures. Therefore, there has been a paradigm shift from the concept of "one drug fits all to right drug for the right patient at the right dose and time." ,
The concept of personalized medicine was recognized by Sir William Osler (1849-1919) who stated that "variability is the law of life and since no two faces are alike, and no two bodies are same and no two individuals behave and react alike under the abnormal circumstances we know as disorder." , According to the US National Cancer Institute, personalized medicine is defined as "a branch of medicine that utilizes information about a person's genetic information and environmental factors to prevent, diagnose and manage the disease."  Another aspect of personalized medicine is addressing to the whole person in relation to personal, medical history and life circumstances. The motive for the evolution of personalized medicine is mainly consumer demand for safe and more effective drugs, faster time to cure, and economic health care.
One of the major influences to the concept of personalized medicine is pharmacogenomics. This is in recent times a burgeoning (flourishing) field which stems (stalks) from the fusion (blending or unification) of pharmacogenetics with genomics. It is a field that encompasses (comprise) the study of genetic polymorphisms that directionalize individual differences in drug response.  Pharmacogenetics can be defined as the study of heredity and the response to drugs whereas pharmacogenomics is the application of whole genome technologies for predicting an individual's sensitivity or resistance to a particular drug. 
A number of genes play a major role in drug response and toxicity. The existence of millions of genetic variations and identifying all of them could take many years. In addition, one person's response to a medication might not be determined by a solitary gene but by many genes interacting with each other.  Variations in genes that encrypt drug metabolizing enzymes drug transporters or drug targets is highly complex and can be categorized into four classes, namely, inefficacy, efficacy, resistance, and toxicity. Polymorphism in the cytochrome P450 (CYP) enzyme has an impact on the fate of pharmaceutical drugs. , CYP is affiliated with multigene family of heme-containing enzymes found predominantly (primarily or chiefly) in the liver that are responsible for the metabolic elimination of most of the drugs currently being used in medicine. 
The activation of procarcinogens and promutagens in the human body principally depends on these enzymes. This is important for drugs, particularly lipophilic drugs such as central nervous system (CNS) active drugs, which generally must be lipophilic to penetrate the blood-brain barrier. The P450 metabolism provides the primary means of these drug elimination because the abovementioned drugs have minimal renal excretion. This large family of genes have been extensively studied, and among the numerous P450 subtypes, CYP2D6, 3A4/3A5, IA2, 2EI, 2C9 and 2C19 play particularly decisive roles in genetically determined responses to a broad spectrum of drugs  particularly in warfarin, Vitamin K epoxide reductase complex protein 1 (VKORC1), and Trastuzumab. 
| Clinical Applications of Personalized Medicine|| |
The existence of significant variations among individuals with the same type of disease suggests that genetic factors play a decisive role in disease pathogenesis. The incorporation of the concept of personalized medicine in the health care system could allow the patients and doctors to become aware of the underlying disease even before the development of clinical signs and symptoms. This in turn leads us to undertake prophylactic preventive measures and treatment prior to the onset of clinical symptoms; this may delay the disease onset and reduce the severity of the symptoms.
By stratifying patients into unique subgroups based on their specific molecular characteristics, personalized medicine aids in planning the treatment.  It also avoids unnecessary side effects and toxicity of treatment in individuals who are predicted to be nonresponders to a particular targeted therapy. By this modality, nonresponders could be stratified into alternate subgroups for personalized therapy.
Furthermore, an expectation of who will respond and who will not respond to a particular treatment will have a considerable effect on how clinical trials are designed and carried out, resulting in reducing their costs and failures. Ultimately, personalized medicine is expected to result in an overall reduction in the cost of health care making it more economical. It is also beneficial for pharmaceutical companies from personalized medicine which are looking to identify target molecules for drug design. This helps them to reduce the duration and costs of clinical trials and potentially revive drugs that were previously thought to be ineffective. 
Oncology is one of the specialties which has derived the greatest benefit from personalized medicine. Cancer is a condition of heterogeneous nature and may be life threatening, where the treatments are expensive and is associated with many adverse events. In cancer, genetics play a major role in the etiopathogenesis. With the omics discipline, the onset of cancer can be prevented in patients and their family members through genetic screening by taking prophylactic measures. Personalized medicine not only helps in identifying the risk of cancer but also to classify the tumor by molecular signaling pathways. This also helps in predicting the effectiveness and resistance of the drug, thereby determining and improving the overall survival rate of the individual. 
In addition to oncology, many pharmacogenomic studies have also been conducted in other diseases such as cardiovascular diseases, CNS disorders, autoimmune diseases and certain infectious diseases.  It has been observed that some patients who have variants in CYP2D6 failed to convert codeine to morphine leading to insufficient analgesia with many adverse effects, whereas patients who have multiple copies of CYP2D6 gene metabolize the drug rapidly resulting in morphine intoxication. Oral diseases such as temporomandibular disorders and orofacial pain are diseases which are more apt for personalized medicine because of uncertain treatment outcome and resistance, as well as a high impact consequences of inappropriate treatment. ,
The approach of pharmacogenetics is still pretty much in its infancy despite its discovery dating back to the 1960s. Despite the direct relevance of genetic polymorphisms in drug response and repeated claims of the benefits of applying pharmacogenetics to personalized medicine, pre-prescription genetic screening is not a routine practice and is largely confined to teaching hospitals and specialized laboratories.  However, the mutational screening using the current state of art technology is still laborious and time consuming and has hassles of having to courier samples to an external laboratory. Moreover, physicians in clinical practice have not been adequately educated in this field. The concept of genomics and personalized medicine have not been incorporated in the curriculum worldwide; thus, bridging the gap between basic science and medicine requires the collaborative efforts of researchers and clinicians. 
Ethical and moral concerns that arise in the heart of genetic testing are the factors that hinder the development of personalized medicine. Deciphering of the genetic code may pose a combination to the protection of one's privacy. Moreover, some irregulars that predict drug response are also markers for disease predisposition. This may subsequently lead to medicolegal implications, such as issuing the data confidentially and the possibility of stigmatization; i.e., whether employer and insurance companies should be given the right to assess the genetic data and the possibility of information falling into the hands of unauthorized parties. Another factor that pose hurdle to the practice of personalized medicine is the undeniable fact that along with the advances in medicine, medical cost is increasing at a rapid rate. The additional cost incurred by a prescription genetic test may increase the financial burden on the consumer.
The abovementioned limitations are some of the concerns that one has to bear in mind before implementing personalized medicine. However, all these drawbacks will be far offset by the potential benefits derived from individualized treatment, such as more effective treatment, reduced incidence of adverse drug reactions and improved quality of care of the patient.  In spite of the concerns mentioned above, personalized medicine is in its way ahead. It is a melding of traditional (e.g., personalized history, examination, and laboratory tests) and novel approaches (e.g., genotyping, genomic evaluations). It uses the science of prediction, modern therapeutics principles, and prevention, which optimize active participation of patients in their care. Treating the patient as a person and not just their illness is also an emotional element of this approach. 
Personalized or molecular medicine has brought tremendous progress in the understanding and management of diseases over the past decade and the concept of personalized medicine will have a significant impact on medical and dental practice, and is being gradually included as an integral component of management plan. This inevitably will result in effective treatment and reducing side effects for patients and will also have the motivation to engage in lifestyle choices and maintenance of health to compensate for their genetic susceptibilities. The introduction of personalized medicine requires a very large initial investment, but with it comes the promise of a rewarding and cost-effective future for medical practice.  Hence, rapid progress in the field of genomics and other omics disciplines may result in a future where the patients get their own genomic sequence in a smart card or memory stick for the right treatment.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Gluttmacher EA, Collins FS. Genomic Medicine - A Primer. N Engl J Med 2002;347:1512-20.
Vogenberg FR, Barash CI, Pursel M. Personalized medicine: Part I: Evolution and development into theranostics. P T 2010;35:560-7.
Clayton EW. Ethical, legal and social implications of genomic medicine. N Eng J Med 2003;349:562-9.
Eng G, Chen A, Vess T, Ginsburg GS. Genome technologies and personalized dental medicine. Oral Dis 2012;18:223-35.
Slavkin HC. The human genome, implications for oral health and diseases and dental education. J Dent Educ 2001;65:463-79.
Marian AJ. Surprises of the genome and personalized medicine. J Am Coll Cardiol 2008;51:456-8.
de Leon J. Pharmacogenomics: The promise of personalized medicine for CNS disorders. Neuropsychopharmacology 2009;34:159-72.
Getting EA, Hart TC. Genetics in dental practice: Social and ethical issues surrounding genetic testing. J Dent Edu 2003;67:550-62.
Chen R, Snyder M. Promise of personalized omics to precision medicine. Wiley Interdiscip Rev Syst Biol Med 2013;5:73-82.
Tanke HJ. Genomics and proteomics: The potential role of oral diagnostics. Ann N Y Acad Sci 2007;1098:330-4.
Emmert-Streib F. Personalized medicine: Has it started yet? A reconstruction of the early history. Front Genet 2013;3:313.
Evans WE, Mc Lead HL. Pharmacogenomics - Drug disposition, drug targets and side effects. N Engl J Med 2003;348:538-49.
Slavkin HC. Implications of pharmacogenomics in oral health. Pharmacogenomics J 2002;2:148-51.
Spear BB, Heath-Chiozzi M, Huff J. Clinical application of pharmacogenetics. Trends Mol Med 2001;7:201-4.
Sadee W, Dai Z. Pharmacogenetics/genomics and personalized medicine. Hum Mol Genet 2005;14:R207-14.
Abrahams E, Ginsburg GS, Silver M. The personalized medicine coalition: Goals and strategies. Am J Pharmacogenomics 2005;5:345-55.
Hong KW, Oh B. Overview of personalized medicine in the disease genomic era. BMB Rep 2010;43:643-8.
Diamandis M, White NMA, Yousef GM. Personalized medicine: Marking a new epoch in cancer patient management. Mol Cancer Res 2010;8:1175-87.
Mancinelli L, Cronin M, Sadee W. Pharmacogenomics: The promise of personalized medicine. AAPS PharmSci 2000;2:E4.
Koo SH, Lee EJ. Pharmacogenetics approach to therapeutics. Clin Exp Pharmacol Physiol 2006;33:525-32.
Xie HG, Frueh FW. Pharmacogenomics step toward personalized medicine. Personalized Med 2005;2:325-37.
Wolf CR, Smith G, Smith RL. Science, medicine, and the future: Pharmacogenetics. BMJ 2000;320:987-90.
Touw DJ. Clinical implications of genetic polymorphisms and drug interactions mediated by cytochrome P450 enzymes. Drug Metab Drug Interact 1997;14:55-82.
Chouchane L, Mamtani R, Dallol A, Sheik JI. Personalized Medicine: A Patient-centered Paradigm. J Translat Med 2011;9:206.
Ginsburg GS, McCarthy JJ. Personalized medicine: Revolutionizing drug discovery and patient care. Trends Biotechnol 2001;19:491-6.
Overdevest JB, Theodorescu D, Lee JK. Utilizing the molecular gateway: The path to personalized cancer management. Clin Chem 2009;55:684-97.
Nair SR. Personalized Medicine: Striding from genes to medicine. Perspect Clin Res 2010;4:146-50.
Giannobile WV, Kornman KS, Williams RC. Personalized medicine enters dentistry: What might this mean for clinical practice. J Am Dent Assoc 2013;144:874-6.
Kornman KS, Duff GW. Personalized Medicine: Will dentistry ride the wave or watch from the beach? JDR Clin Res 2012;91(Suppl 1):8S-11S.