lumacaftor--ivacaftor-drug-combination and Leukemia--Myeloid--Acute

Drug toxicity and efficacy are difficult to predict partly because they are both poorly defined, which I aim to remedy here from a transcriptomic perspective. There are two major categories of drugs: (1) restorative drugs aiming to restore an abnormal cell, tissue, or organ to normal function (e.g., restoring normal membrane function of epithelial cells in cystic fibrosis), and (2) disruptive drugs aiming to kill pathogens or malignant cells. These two types of drugs require different definition of efficacy and toxicity. I outlined rationales for defining transcriptomic efficacy and toxicity and illustrated numerically their application with two sets of transcriptomic data, one for restorative drugs (treating cystic fibrosis with lumacaftor/ivacaftor aiming to restore the cellular function of epithelial cells) and the other for disruptive drugs (treating acute myeloid leukemia with prexasertib). The conceptual framework presented will help and sensitize researchers to collect data required for determining drug toxicity.

Topics: Aminophenols; Aminopyridines; Animals; Antineoplastic Agents; Benzodioxoles; Cell Death; Cystic Fibrosis; Dose-Response Relationship, Drug; Drug Combinations; Drug Development; Epithelial Cells; Gene Expression Profiling; Gene Regulatory Networks; Humans; Leukemia, Myeloid, Acute; Pyrazines; Pyrazoles; Quinolones; Toxicity Tests; Transcriptome