Since ancient times medicine has always aspired to be personalized. Even Hippocrates combined an assessment of the four humours—blood, phlegm, yellow bile, and black bile—to determine the best course of treatment for each patient.
Today, personalized medicine stands for utilizing the information about a person’s genes, proteins, and environment to prevent, diagnose, and treat disease. Personalized Medicine aims to customize treatment to every patient based on one’s genetic make up. And it was only after the complete human gene was sequenced in 2001 that Personalized Medicine took off in a big way; today there are more than 15,000 tests for more than 2,800 genes.
Though the clinical benefits of personalized medicine are still evolving; broadly five areas hold most promise
• Diagnosis/Prognosis — to assess particular subtypes of a disease or the unique characteristics of a condition
• Treatment prediction — to analyze whether a patient, infectious agent or tumor with particular characteristics will respond to a certain treatment
• Dosing — to determine appropriate amounts or strengths of treatment to administer to a particular individual
• Safety — to anticipate adverse treatment reactions in certain subpopulations
• Predictive — To determine the persons risk for certain disease, thereby modifying lifestyle factors or undertaking prophylactic therapy to decrease the risk or prevent it completely
Let us understand Personalized Medicine with a few examples in each of the areas.
- Trastuzumab (Herceptin®) was the first genetically-guided therapy for the treatment of metastatic breast cancers which were HER 2 gene positive. Today, HER2 testing is a routine part of clinical diagnosis for breast cancer patients.
- Ckit gene mutation (genetic change) testing is a confirmatory diagnostic test for Gastrointestinal stromal tumor and also helps in selecting the right candidates for anti EGFR (epidermal growth factor receptor) therapy.
- Patients with colon cancer which has metastasized (spread) may not respond to certain drugs such as Cetuximab if they have a mutated (genetic change) form of the KRAS gene
- A certain drug Crizotinib which is indicated in the treatment of lung cancer (non small cell type) will be effective only in those patients who infact show an abnormal form of the gene called as the anaplastic lymphoma kinase (ALK) gene.
- Persons who have a variation in the gene called CYP2C19 are recommended higher doses of the drug Clopidogrel or maybe even an alternative therapy. This is because the variation in the gene does not permit them to efficiently utilize the drug. Clopidogrel is generally given to prevent blood clots in stent patients
- Individuals who are positive for the Hepatitis C virus (resulting in a form of jaundice) with a specific genotype /genetic change in the IL28B gene will need higher doses of anti virals, more aggressive treatment for a relatively longer period of time. Having prior information about this has helped the clinicians pre-empt the expected duration of the treatment and ensure greater adherence to treatment regimen.
Thiopurines is a category of drugs widely used in the treatment of blood cancers and certain autoimmune disorders. Variation in the genetic makeup of the enzyme thiopurine methyl transferase (TPMT) which is responsible for metabolizing the thiopurines, results in increased toxicity. Lower dosage or non-purine agents are then suggested as alternative.
The genotyping of drug-metabolizing enzymes (cytochrome P450’s) has produced improved dosing of drugs for conditions as wide-ranging as depression and anxiety. This has helped patients avoid harmful side effects, adverse drug interactions, or ineffective treatment.
- Women with certain BRCA1 or BRCA2 gene variations have up to an 85 percent lifetime chance of developing breast cancer, compared with a 13 percent chance among the general female population. These women also have up to a 60 percent chance of developing ovarian cancer, compared with a 1.7 percent chance among the general female population. The BRCA1 and BRCA2 genetic test can guide preventive measures, such as increased frequency of mammography, prophylactic surgery, and chemoprevention.
- A 23-gene blood RNA signature used to screen/predict for obstructive coronary artery disease
- The IL-1 genetic test (PerioPredict®) plus two other risk factors to guide the frequency of care to prevent periodontitis, one of the most common chronic inflammatory diseases.
- Genetic markers at the CDKN2A/2B (cyclin dependent kinase genes) to predict risk to complex multifactorial disease like Coronary artery disease are also being offered. These markers help evaluate the risk over and above traditional risk factors, such as smoking, hypertension and diabetes, and allow the opportunity for refining risk stratification and provides the critical lead time for the individual to take pre-emptive and precautionary measures.
However personalized medicine also faces certain challenges and responsibilities. The challenges are at present our ability to collect genetic data, outpaces the medical community’s ability to understand and act on it. To put it simplistically we know about the gene sequence (genotype) but we are still gaining information about how it manifests (i.e. phenotype) differently in different individuals and also the gene-environment interaction. There is thus an urgent need to conduct robust translational studies with well defined cohorts for genotype-phenotype correlation.
Another area of concern is often specialized diagnostics tests and services are linked with personalized medicine and the role of the diagnostic provider becomes critical, especially when one considers the consequences of misinterpretation. This reinforces the importance of lab accreditation by regulatory authorities and the importance of scientific, intellectual capabilities and quality control criteria for diagnostic providers.
A part of the challenge is also the need to encourage Drs to adopt it in practice in order to get it to the patients. And the responsibility lies in moving genomics training from classroom to clinic as an essential feature of new approach to medical education.
The impact of Personalized Medicine in India is gaining momentum, and is in routine clinical practice in oncology. However the adoption of Personalized Medicine has been slower than expected, because first and foremost it is viewed as expensive, there is the lack of exposure to molecular biology among doctors, some of the test results for Personalized Medicine may have longer turnaround times, lack of skilled manpower and the smaller market size; and hence the lack of investment in marketing and promoting these tests, as some of the key challenges impacting the growth.
Also many patients and their health care providers are uncertain about the value of Personalized Medicine, so there isn’t yet a high demand for these novel approaches to care. Also people have to understand that “cost-effective” is not synonymous with “cost savings.” Personalized Medicine provides dividends in terms of improved health rather than reduced wasteful spending.