3 min read
DNA Strand

The Role of PGx in Improving Translational Medicine

Pharmacogenetics and pharmacogenomics can play an important role in improving the evolving field of translational medicine.

“Translational medicine or research, an emerging discipline on the frontier of basic science and medical practice, has the potential to enhance the speed and efficiency of the drug development process through the utilization of pharmacogenetics and pharmacogenomics,” wrote Willard H. Dere, M.D., and Tamas S. Suto, M.D.

Dere and Suto are experts in the translational medicine field with Dere co-director of the Utah Center for Clinical and Translational Science at the University of Utah’s School of Medicine, and Suto senior vice president and head of global medical affairs oncology for Merck.

What is Translational Medicine?

Translational medicine is sometimes referred to as translational science or translational research.

If there is a unifying principle to the three terms it would be that the ultimate purpose is to improve human health via a “bench to bedside” approach, according to the American Society for Clinical Pharmacology & Therapeutics.

Let’s look at two definitions of translational medicine to gain a deeper understanding of the discipline:

Models of translational medicine are often based on the three T’s of the translational pipeline:

  1. T1 Translation to Humans: Developing treatments and interventions. This phase includes observational studies, case studies as well as Phase I and II clinical trials.
  2. T2 Translation to Patients: Testing the efficacy and effectiveness of these treatments and interventions. This phase includes Phase III clinical trials, observational studies plus evidence synthesis and guidelines development.
  3. T3 Translation to Practice: Dissemination and implementation research for system-wide change. This phase includes dissemination research, implementation research, diffusion research and Phase IV clinical trials.

Nuances of Pharmacogenetics vs. Pharmacogenomics

While some publications will use pharmacogenomics (PGx) interchangeably with pharmacogenetics, there is a nuance between the two terms and fields of study they represent.

Dere and Suto defined the two as:

  • Pharmacogenetics is the study of genetic causes of individual variations in drug response.
  • Pharmacogenomics deals with the simultaneous impact of multiple mutations in the genome that may determine the patient’s response to drug therapy.

Together, pharmacogenetics and pharmacogenomics, can improve translational medicine.

“The utilization of these methods in the drug development process may therefore identify patient sub-populations that exhibit more effective responses and/or an improved benefit/risk profile upon treatment,” write Dere and Suto.

Important Role of Genetics in Patients Response to Drugs

Pharmacogenetics and Pharmacogenomics are promising translational medicine tools because of the important role that genetics play in how patients respond to drugs.

The authors of a study of “Pharmacogenetics of Asthma” in the American Journal of Respiratory and Critical Care Medicine found that genetic variants may alter response to drugs in three main ways:

  • Variation in metabolism of a drug among individuals, especially in enzymes involved in the catabolism or excretion of a drug
  • Variance among population members with respect to drug adverse effects that are not based on the drug’s action
  • Genetic variance in the drug treatment target or target pathways

“Both pharmacogenetics and pharmacogenomics can provide these insights: the former focuses on the impact of a single gene mutation and the latter on the simultaneous impact of multiple mutations that may determine the drug’s efficacy and toxicity,” say Dere and Suto.

Improving Decision-Making Process During Drug Development

Translational medicine, with the help of PGx, can improve the decision-making process during drug development for various areas including cardiovascular, asthma, oncology, and osteoporosis.

“The effect of genetics on how some drugs are metabolized has been known for years. Genetic variants of drug metabolizing enzymes have been identified that explain differences between individuals in drug concentrations and their corresponding pharmacodynamic, including safety, effects,” write Dere and Suto.

Diseases and recognized drug metabolizing enzymes involve common disorders and treatments such as:

  • Depression (tricyclic antidepressants, selective serotonin reuptake inhibitors)
  • Cardiovascular disease (beta blockers, angiotensin 1 receptor inhibitors)
  • Thromboembolic disorders with coumarin anticoagulants
  • Ulcer disease with proton pump inhibitors
  • Malignant disease (thiopurines, 5 fluorouracil, irinotecan)
  • Tuberculosis (isoniazid)

Dere and Suto also cite other examples where genotyping procedures can be potentially valuable in translational research including:

  • Metoprolol and congestive heart failure
  • Human epidermal growth factor receptor 2 (HER2) in breast cancer
  • Epidermal growth factor receptor (EGFR) kras in colorectal cancer
  • Gefitinib (Iressa) in contrasting efficacy responses in non-small cell lung carcinoma
  • Oncology therapeutic, panitumumab, for metastatic colorectal cancer
  • Asthma patients profiled to proclivity to produce leukotrienes
  • Asthma patients and polymorphisms in the beta-2 receptor

“The implications of using pharmacogenetic-pharmacogenomic testing to stratify patient groups during translational and later stage development could be substantial as a molecule becomes a registered therapeutic for a specific disease,” concluded Dere and Suto. “Pharmacogenetics and pharmacogenomics should therefore improve our ability to customize patient-specific strategies to predict, prevent, diagnose, and treat disease leading to individualized treatments.”

Contact WiseDX today to learn more about their pharmacogenomics tests based on advanced molecular assay technologies, which are expected to support physicians in offering better informed clinical decisions, especially for those in nursing homes and long-term care facilities.