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PHARMACOGENOMICS: Driving Personalized Medicine

Wolfgang Sadee, Danxin Wang, Katherine Hartmann and Amanda Ewart Toland
Pharmacological Reviews March 16, 2023, PHARMREV-AR-2022-000810; DOI: https://doi.org/10.1124/pharmrev.122.000810
Wolfgang Sadee
1Cancer Biology and Genetics, Ohio State University, United States
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  • For correspondence: Wolfgang.sadee@gmail.com
Danxin Wang
2Pharmacotherapy and Translational Research, University of Florida, United States
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Katherine Hartmann
3University of Pennsylvania, United States
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Amanda Ewart Toland
4The Ohio State University, United States
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Abstract

Personalized medicine tailors therapies, disease prevention, and health maintenance to the individual, with pharmacogenomics serving as a key tool to improve outcomes and prevent adverse effects. Advances in genomics have transformed pharmacogenetics, traditionally focused on single gene-drug pairs, into pharmacogenomics, encompassing all 'omics' fields, e.g., proteomics, transcriptomics, metabolomics, and metagenomics. This review summarizes basic genomics principles relevant to translation into therapies, assessing pharmacogenomics' central role in converging diverse elements of personalized medicine. We discuss genetic variations in pharmacogenes (drug-metabolizing enzymes, drug transporters, and receptors), their clinical relevance as biomarkers, and the legacy of decades of research in pharmacogenetics. All types of therapies, including proteins, nucleic acids, viruses, cells, genes, and irradiation, can benefit from genomics, expanding the role of pharmacogenomics across medicine. FDA approvals of personalized therapeutics involving biomarkers increase rapidly, demonstrating the growing impact of pharmacogenomics. A beacon for all therapeutic approaches, molecularly targeted cancer therapies highlight trends in drug discovery and clinical applications. To account for human complexity, multi-component biomarker panels encompassing genetic, personal, and environmental factors can guide diagnosis and therapies, increasingly involving artificial intelligence to cope with extreme data complexities. However, clinical application encounters substantial hurdles, such as unknown validity across ethnic groups, underlying bias in health care, and real-world validation. This review will address the underlying science and technologies germane to pharmacogenomics and personalized medicine, integrated with economic, ethical, and regulatory issues - providing insights into the current status and future direction of health care.

Significance Statement Personalized medicine aims to optimize health care for the individual patients with use of predictive biomarkers to improve outcomes and prevent adverse effects. Pharmacogenomics drives biomarker discovery and guides the development of targeted therapeutics. This review addresses basic principles and current trends in pharmacogenomics, with large-scale data repositories accelerating medical advances. The impact of pharmacogenomics is discussed, along with hurdles impeding broad clinical implementation, in the context of clinical care, ethics, economics, and regulatory affairs.

  • cancer
  • developmental pharmacology
  • drug metabolism
  • drug-drug interactions
  • gene regulation/transcription
  • Genetic polymorphisms
  • pharmacogenetics/pharmacogenomics
  • systems pharmacology
  • Copyright © 2023 American Society for Pharmacology and Experimental Therapeutics

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Pharmacological Reviews: 75 (2)
Pharmacological Reviews
Vol. 75, Issue 2
1 Mar 2023
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OtherReview Article

PHARMACOGENOMICS: Driving Personalized Medicine

Wolfgang Sadee, Danxin Wang, Katherine Hartmann and Amanda Ewart Toland
Pharmacological Reviews March 16, 2023, PHARMREV-AR-2022-000810; DOI: https://doi.org/10.1124/pharmrev.122.000810

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OtherReview Article

PHARMACOGENOMICS: Driving Personalized Medicine

Wolfgang Sadee, Danxin Wang, Katherine Hartmann and Amanda Ewart Toland
Pharmacological Reviews March 16, 2023, PHARMREV-AR-2022-000810; DOI: https://doi.org/10.1124/pharmrev.122.000810
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