From Mechanism to Prediction: Translational Approaches to Drug-Induced Organ Toxicity by Chemotherapeutics and Biologic Therapies

Drug-induced organ toxicity remains a leading cause of attrition during drug development and of post-market safety withdrawals. The liver, kidney, heart, and nervous system are the organs most frequently affected by chemotherapeutic agents and biologic therapies (e.g., anthracyclines, taxanes, CAR-T and other cell-based immunotherapies), where mechanistic pathways vary substantially depending on drug class, dosing regimen, and patient population. Preclinical models have historically struggled to predict human organ-level responses with sufficient fidelity, generating both false positives that halt viable compounds and false negatives that reach patients. Advances in microphysiological systems, multi-omics profiling, and computational toxicology are beginning to close this gap, but their systematic integration into regulatory and clinical decision-making remains incomplete. Translational pharmacology sits at the intersection of these efforts, connecting mechanistic insight at the cellular and molecular level to clinically meaningful toxicity prediction.A central challenge in drug safety science is the disconnect between mechanistic understanding of toxicity and the ability to predict its occurrence, severity, and reversibility in human subjects. Existing biomarkers for organ injury are often insensitive to early-stage damage or lack mechanistic specificity, and preclinical-to-clinical translation frequently fails because animal models do not recapitulate human pharmacokinetics or organ biology with sufficient accuracy. This Research Topic brings together work that addresses this translational gap directly, focusing on research that links mechanistic toxicology and prediction, rather than treating either in isolation. Contributions are sought that show how specific molecular or cellular mechanisms of drug-induced injury can be used to develop predictive tools, including biomarkers, computational models, in vitro systems, or clinical decision frameworks, with a focus on toxicity arising from cytotoxic chemotherapeutics and biologic/cell-based therapies, applicable across one or more organ systems affected. The collection is particularly interested in findings with direct implications for drug development, regulatory toxicology, or clinical pharmacovigilance, applicable across one or more organ systems affected by drug toxicity.This Research Topic welcomes contributions focused on the mechanistic basis and translational prediction of organ toxicity induced by chemotherapeutic agents and biologic therapies, including but not limited to hepatotoxicity, nephrotoxicity, cardiotoxicity, and peripheral/central neurotoxicity. Relevant themes include mechanistic biomarker discovery and validation, organ-on-a-chip and microphysiological systems applied to toxicity assessment, multi-omics approaches to toxicity characterization, computational and machine learning models for toxicity prediction, species translation and the limitations of animal models, early clinical signals of chemotherapy- or biologic-induced organ injury in pharmacovigilance and clinical trial datasets, and pharmacokinetic/pharmacodynamic determinants of toxicity risk.Manuscript types accepted include Original Research, Review, Mini Review, Methods, Hypothesis and Theory, Perspective, and Opinion articles, consistent with the Translational Pharmacology section’s article types. Case Report submissions are welcome per section policy; Topic Editors will prioritize those offering mechanistic insight relevant to the topic’s scope. In line with the section’s general exclusions, this Research Topic will not consider meta-analyses or cohort studies.Topic Editor Dr. John Oluwafemi Teibo Co-Founder and Chief Scientific Officer (CSO) of ABMIUM Ltd. The other Topic Editors declare no competing interests with regard to the Research Topic subject. Topic editors: Anne Adeyanju, Olorunfemi Raphael Molehin, John Oluwafemi Teibo, Jeffrey Pradeep Raj Source: https://www.frontiersin.org/research-topics/84225/from-mechanism-to-prediction-translational-approaches-to-drug-induced-organ-toxicity-by-chemotherapeutics-and-biologic-therapies