Pharmacogenomic research provides valuable insight into how individuals respond to existing and new therapies, and pharmacogenomic biomarkers show great promise in predicting drug response and guiding drug choice and dosage.
The AAPS Journal open access review article Pharmacogenomic Biomarkers for Improved Drug Therapy—Recent Progress and Future Developments, by Volker M. Lauschke, Lili Milani, and Magnus Ingelman-Sundberg, “review[s] the evolutionary background of genetic polymorphisms in drug-metabolizing enzymes, provide[s] some important examples of current use of pharmacogenomic biomarkers, and give[s] an update of germline and somatic genome biomarkers that are in use in drug development and clinical practice.”
The use of next-generation sequencing in precision medicine. Genomic DNA (gDNA) is isolated from tissue biopsies (somatic genome) or from blood samples (germline genome) and libraries for downstream sequencing applications are prepared. Optionally, a target capture step can be performed to enrich for genomic intervals of interest and to reduce required sequencing capacity. Subsequent to sequencing, genetic variants in the sample (indicated by red arrow) are identified by comparison to a relevant reference, which can be either the human reference genome or, in the case of tumor biopsies, the germline genome from the same patient. The functional consequence of identified variants can be predicted based on preexisting experimental data or if such information is not available by using computational algorithms
Pharmacogenomic biomarkers are especially being used in oncology. Every tumor has unique genetic variants and cancer genomics. Oncological therapies can be tailored per patient based on the genetic differences between tumor and non-tumor cells. Almost 30 targeted cancer drugs have been approved so far as a result of pharmacogenomic research.
The authors also discuss known genetic variants that affect the efficacy and/or toxicity of the drugs codeine, warfarin, abacavir, azathioprine, simvastatin, and fluorouracil.
With the current emphasis on precision medicines, pharmacogenomic research is key in determining rare genetic variants and adjusting treatment plans accordingly. Pharmacogenomic biomarkers are already helping in the development of personalized treatment plans, and additional research will only improve treatment options.
This review article won the 2020 AAPS Journal High Impact Article Award for its exceptional impact on the pharmaceutical sciences. It has been downloaded almost 9,000 times and has received 45 citations as of February 2021.
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