Untangling the Genetic Basis of Drug Response

Rohde, Palle Duun; Kristensen, Torsten Nygaard

doi:10.2217/pgs-2019-0155

Cited by 2 publications

(2 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This may severely impact on the responses to medical treatment and it has been suggested, that 20-90% of the variation seen in the response to a medicine in humans is attributable to genetic differences among patients [18]. Such knowledge is a driver of the rapidly developing field of precision medicine [19]. However, in the process of testing a new drug it is standard practice to investigate its efficiency and potential unwanted side effects on one or few genetic backgrounds of cell cultures or laboratory species.…”

Section: Introductionmentioning

confidence: 99%

Genotype and Trait Specific Responses to Rapamycin Intake in Drosophila melanogaster

Rohde

Bøcker

Jensen

et al. 2021

Insects

Self Cite

View full text Add to dashboard Cite

Rapamycin is a powerful inhibitor of the TOR (Target of Rapamycin) pathway, which is an evolutionarily conserved protein kinase, that plays a central role in plants and animals. Rapamycin is used globally as an immunosuppressant and as an anti-aging medicine. Despite widespread use, treatment efficiency varies considerably across patients, and little is known about potential side effects. Here we seek to investigate the effects of rapamycin by using Drosophila melanogaster as model system. Six isogenic D. melanogaster lines were assessed for their fecundity, male longevity and male heat stress tolerance with or without rapamycin treatment. The results showed increased longevity and heat stress tolerance for male flies treated with rapamycin. Conversely, the fecundity of rapamycin-exposed individuals was lower than for flies from the non-treated group, suggesting unwanted side effects of the drug in D. melanogaster. We found strong evidence for genotype-by-treatment interactions suggesting that a ‘one size fits all’ approach when it comes to treatment with rapamycin is not recommendable. The beneficial responses to rapamycin exposure for stress tolerance and longevity are in agreement with previous findings, however, the unexpected effects on reproduction are worrying and need further investigation and question common believes that rapamycin constitutes a harmless drug.

show abstract

Section: Introductionmentioning

confidence: 99%

Genotype and Trait Specific Responses to Rapamycin Intake in Drosophila melanogaster

Rohde

Bøcker

Jensen

et al. 2021

Insects

Self Cite

View full text Add to dashboard Cite

show abstract

“…Though these considerations pertain to pharmacokinetic phenotypes, they do not necessarily apply to the analysis of pharmacodynamic outcomes, including drug response, which may well have more complex, polygenic genetic architectures given their multifactorial aetiology (Roden et al, 2019;Rohde and Kristensen, 2020). Robust pharmacogenomic analyses of response to psychiatric drugs are pressingly needed, as no replicated pharmacodynamic associations have yet been found (Bousman et al, 2021).…”

Section: Pharmacogenomic Phenotypes: Simple Trait Genomics?mentioning

confidence: 99%

Pharmacogenomics: A road ahead for precision medicine in psychiatry

Pardiñas¹,

Walters²

2021

Neuron

View full text Add to dashboard Cite

Untangling the Genetic Basis of Drug Response

Cited by 2 publications

References 20 publications

Genotype and Trait Specific Responses to Rapamycin Intake in Drosophila melanogaster

Genotype and Trait Specific Responses to Rapamycin Intake in Drosophila melanogaster

Pharmacogenomics: A road ahead for precision medicine in psychiatry

Contact Info

Product

Resources

About