Pharmacoexposomics framework integrates environmental metabolomics with pharmacogenomics via high-resolution mass spectrometry
The study introduces pharmacoexposomics as a conceptual framework that integrates pharmacogenomics with high-resolution mass spectrometry to quantify metabolic responses to drugs and environmental exposures. Investigators outline the IndiPHARM platform, an ARPA-H-supported initiative designed to combine population-scale exposomic and genomic data with clinical records to explain interindividual variability in drug efficacy and toxicity. The proposed approach aims to identify adverse drug reactions and inform tailored treatment strategies. For clinical laboratories, the framework underscores the expanding utility of untargeted metabolomics and mass spectrometry as complementary tools to genetic testing in precision medicine.
The original study
Pharmacoexposomics: The Environmental Complement to Pharmacogenomics to Advance Precision Medicine.
- Authors
- Reho P, Thaker VV, Athreya AP, Cremers S, Go YM, Hripcsak G, et al.
- Journal
- Annual review of pharmacology and toxicology
- Type
- Journal Article, Review
- PMID
- 42594291
Original abstract
Despite advances in pharmacogenomics that have led to innovative therapeutic strategies, substantial interindividual variability in drug efficacy and toxicity persists. Both endogenous and exogenous factors contribute to this unexplained variation, resulting in suboptimal treatment effectiveness, unnecessary healthcare costs, preventable mortality, and significant human suffering. The emerging field of exposomics is aimed at addressing the complex exposures that impact human health and offers an opportunity to interrogate how these exposures influence drug actions and outcomes. Here, we introduce pharmacoexposomics as a complementary framework that systematically quantifies the body's metabolic response to drug and environmental exposures using high-resolution mass spectrometry. We then present IndiPHARM (Individualized Pharmacology), a multi-institution, Advanced Research Projects Agency for Health-supported platform designed to integrate population-scale pharmacoexposomics with pharmacogenomics and clinical data to elucidate interindividual variability in drug response, identify adverse reactions, and inform tailored, effective treatment strategies that advance precision medicine.