Pharmacogenomics is the field that explores how genomics and other "omics" contribute to individual differences in drug response. It focuses on using advanced technology to identify genetic variants that impact how individuals respond to medications, with the goal of creating personalized treatment strategies that enhance drug effectiveness and ensure safety. The field aims to clarify how genetic variation influences both the effectiveness and potential side effects of drugs.
Research methods such as genome-wide association studies and studies of specific genes indicate that genetic information can guide the selection of the most suitable drugs and dosages, potentially reducing adverse drug reactions. Over the past 50 years, pharmacogenomics has advanced significantly, driven by developments in DNA sequencing and molecular technologies, greatly improving our understanding of the human genome.
The interaction between drugs and human proteins forms the foundation of drug discovery guided by pharmacogenomics. After identifying, structurally analyzing, and validating a target protein, drugs that have a better fit and higher affinity for this target can be predicted and identified more effectively through high-through put screening and computer-aided drug design. The genomic principle can be used to uncover the molecular causes of diseases at an early stage. Structural pharmacogenomics assists in identifying and validating disease-specific targets for drug action, such as the EGFR signaling pathway and biomarkers like KRAS, RAF, MAPK, PI3K, and AKT, which are relevant for various types of cancer.
Pharmacogenomics links target biomarkers with the underlying causes of diseases to determine how the disease is related to these biomarkers. This connection helps in identifying appropriate drug molecules that can act on the specific target. Chemical genomics examines how genes (genetic biomarkers) respond to drugs (chemicals). Genetic polymorphisms can result in the creation of proteins with modified functions, such as alterations in drug-metabolizing enzymes or drug transporters. These differences can ultimately affect the pharmacokinetic and pharmacodynamic characteristics of the drug.
The list below provides known applications of pharmacogenomics:
• Enhance drug safety and decrease adverse drug reactions (ADRs);
• Customize treatments based on patients' unique genetic predispositions,
including determining the most effective dosages;
• Advance drug discovery with a focus on human diseases;
• Strengthen evidence for the effectiveness of clinical trials.
In oncology, pharmacogenomic tests help identify patients who are most likely to benefit from specific cancer treatments. In behavioral health, these tests assist physicians and caregivers in optimizing medication choices and mitigating side effects. In cardiovascular disorders, the main concern is response to drugs including warfarin, clofidograil, beta blockers, and stains.
Taking inspiration from Danish physicist Niels Bohr’s insightful remark, "Prediction is very difficult, especially about the future," I do not aim to forecast the future of pharmacogenomics. Instead, I would like to share some broad observations from a personal standpoint regarding the opportunities and challenges that researchers in this field may encounter moving forward.
This article is taken from the Galen Gazette, August 2024, Issue
No. 04. The author,
Fakhray Jahan Rimi, is a first-semester pharmacy student at Comilla
University.
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