|Year : 2019 | Volume
| Issue : 1 | Page : 1-3
Department of Medicine, MG Institute of Medical Sciences, Wardha, Maharashtra, India
|Date of Web Publication||14-Mar-2019|
Dr. O P Gupta
Department of Medicine, MG Institute of Medical Sciences, Sevagram, Wardha - 442 102, Maharashtra
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Gupta O P. Personalized Medicine. J Mahatma Gandhi Inst Med Sci 2019;24:1-3
“Genetic Report Cards” will be the future of predicting disease risk. We have the science to quantify our genetic fates at birth – but should we?
– Abby Norman
Throughout the history of humankind, attempts have been made to know or predict the cause of human suffering, whether it be the astrology, i.e., planetary connection to various diseases, “nadi-pareeksha,” testing of body fluids, imaging, or the genomic study of modern times so that it can be relieved by appropriate intervention. Our health is determined by our physical built-up, lifestyle, and environment. Each individual is unique; thus, individual risk of developing a disease and response to therapy may differ. That means for a patient with a particular disease, one has to use different approaches to achieve the best outcome in the prevention or treatment of the disease, i.e., customizations of healthcare.
The marvels of science and technology today have enabled the patient to access the modern facilities in diagnostics and treatment, viz., ultrasound, computed tomography/magnetic resonance imaging scanners, transplantation, and in vitro fertilization fertility treatment, etc., Recent technological and scientific advances have influenced the medical practice so to adapt the developments and take initiatives for everyone's benefit regardless of where they live, the type of illness, and selecting appropriate and optimal therapies based on the patient's molecular analysis. This is what we call personalized medicine.
The ancient science of Ayurveda had characterized the individuals according to their three principles, Vata, Pitta, and Kafa, a traditional approach to understand the disease pattern in each of these groups and to provide treatment accordingly, though they might be having a similar illness. We can say that at that time also there was not a “one size fits all” phenomenon, rather an approach to personalized medicine. Even in modern time, blood transfusion is not only given from a randomly selected donor but also given from the same blood group-matched donor. The personalized medicine thus has been in use since long.
The growth of new diagnostics and informatics, particularly the genomics, has provided the molecular basis of the disease to stratify or group the patients for further personalized management. There are other terms used for the same concepts such as Precision Medicine, P4 Medicine (Predictive, Preventive, Participatory, and Personalized), and Theranostics with little variations. The patient's genetic contents on molecular analysis determine the optimal therapy for an individual patient. The personalized medicine has added another term the “pharmacogenomics” that is, how the genetic makeup of an individual affects his/her response to drugs.
Now, we understand that patients' tumors have genetic changes that cause cancer to grow and spread. Molecular analysis or molecular profiling has broad (whole genome sequencing) and a targeted focus, such as targeted DNA sequencing or multigene panel. It includes genome sequencing which can reveal mutation in DNA that can influence diseases ranging from cystic fibrosis to cancer. Similarly, RNA sequencing can show which RNA molecules are involved with specific diseases. RNA changes occur in response to the environment whereas DNA does not. Whole genome sequencing may be difficult to interpret, since there may be genetic alteration other than those causing cancer, or their effects are still not known. Cancer can be called as a genetic disease in view of such changes, which can be inherited or may develop randomly due to an error in cell division or from exposure to carcinogens.
Recent studies of RNA sequencing have shown changes in its expression, translation, and protein levels as part of genetic differences amongst individuals. Genome-wide association study (GWAS) has helped a physician to correlate the mutations with a particular disease which can subsequently be used to diagnose that disease in other patients, for example, two different mutations were found with variation in only one nucleotide (“single nucleotide polymorphism”) associated with age-related macular degeneration. However, all the genetic changes that can cause cancer to develop, grow, and spread have not been discovered, but researchers are working on it and the new changes discovered every day are forming a large database which can be accessed for other studies. Over 1300 GWASs have been completed.
Molecular studies provide an opportunity for the patients and the healthcare provider to know the risk of disease, response to the therapy, and benefit from more targeted and effective treatment. However, then, the researchers and physicians need to have robust knowledge and understanding of the genomics and other fields related to personalized medicine.
One can know the genetic variation by comparing the individual's DNA sequence with that of reference genome (like Human Genome Project). This also helps the industry to develop more effective and specialized treatment. Recently, the number of private companies (23andMe, Navigenics, and Illumina) has created Direct-to Consumer genome sequencing accessible to the public. Detailed information about individual genome, say the presence of mutation, its impact can be reduced, or the onset of the disease can be delayed, may help prevent adverse events, allow appropriate drug and dosages so to create maximum efficacy with the prescriptions.
Genotyping of drug metabolizing enzymes is also necessary to ascertain the efficacy of the drugs, for example, mutation in CYP 2D6 gene which encodes for metabolizing enzyme resists the breakdown of tamoxifen in some women with breast cancer necessitated the change of the treatment regimen. Similar studies have produced improved dosing of drugs for various conditions such as anxiety and depression, coronary artery and peripheral arterial disease, and inflammatory bowel disease.
What treatment one receives depends on the type of cancer, its size, whether it is localized or has metastasis and may undergo surgery, chemotherapy, radiation therapy, immunotherapy, or combination of these. When one is diagnosed with cancer, he/she is likely to receive the same treatment as the others are getting for the same type of cancer, but response to therapy may be different. Pharmacogenomic research helps us to understand why individuals respond differently to medicines. The field of science and genetics allows us to develop effective, safe medications, and doses tailored to an individual's genetic makeup what we call it today as “targeted therapy” which is either small-molecule drugs or monoclonal antibodies. For example, a patient with lung cancer having Epidermal Growth Factor Receptor gene (that cause rapid cell division) mutation will respond well with EGFR inhibitor drugs.
There can be several limitations as follows:
- DNA alterations may not be related to growth of the tumor
- Alterations identified but cannot be targeted by available therapy
- Body may respond differently to therapy
- Cancer cells have heterogeneous genetic alterations; small biopsy sample may not give a true picture; potential drugs may not be active against all cancer cells leading to continuous growth the other cells
- The genetic alterations in the tumor may change over time
- A given type of cancer, such as breast, lung, and stomach, may have several molecular subtypes, a sort of adverse landscape of genetic alterations
- High-quality biological sample is needed for genomic studies
- A large number of clinical trials are required
- The great challenge is managing and analyzing the vast amount of data
- The cost of tumor sequencing is prohibitive.
The recent information about the discovery that genetic and epigenetic changes in tumor are related to cancer has resulted in the development of therapies that target these changes and the diagnostic tests that identify the patients likely to be benefited from these therapies. In the last decade, the number of research projects has cataloged the genetic changes associated with number of types of cancer. Mutation in HER2 gene has unexpectedly detected in a number of cancers including breast, bladder, pancreas, and ovary.
Currently, 20% of pharmaceutical research is gene-based and available personalized medicine has increased by 62%. Since 2012 and because 70% of cancer drug development is that of precision medicine, the effectiveness of traditional drugs is 60% and adherence after 2 years is 38%.
The new technology and knowledge may investigate the molecular basis of clinical phenotypes. It may distinguish aggressive cancers from the indolent ones. Besides response to therapy, the mechanism of resistance to treatment can also be studied. More clinical trials will provide more tailored approach to cancer diagnosis and treatment as well as improve methods of predicting cancer risk, prognosis, and response to treatment. The molecular signatures may be strong predictors of benefit to humankind.
The future medicine has potential for a wide range of studies and innovations in molecular, genomic, cellular, clinical, behavioral, physiological, and environmental fields. Moreover, many newer applications such as census of distinct type of immune cells, mobile devises providing real-time monitoring of glucose, blood pressure, cardiac rhythm, genotyping for specific disease, blood test detecting circulating tumor cells.
The field of genetics is growing very rapidly, and now even, the mail-in DNA tests are available. A number of companies are offering such tests which can be done with a sample of saliva or a swab of your cheek.
If you are concerned about disease and curious to know, information can be obtained from these tests, whether your genes show the abnormality related to a specific disease, such as Alzheimer's or cancer. However, it cannot tell whether you will really get it or what are the chances to get it since other factors such as your lifestyle, habits also affect it. Moreover, you may get information about the limited number of conditions only. No company can guarantee as of today 100% accuracy. On the one hand, such information can cause anxiety and stress; on the other hand, the maintenance of the privacy of your personal data is questionable.
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