ArticleJACC. CardioOncology2026
CRISPR/Cas9 Screens Implicate RARA and SPNS1 in Doxorubicin Cardiotoxicity.
Article in JACC. CardioOncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
4 citing papers in PubMed.
- When "Uptake" Is Organelle Biology: Derisking CRISPR Anthracycline Cardiotoxicity Screens.JACC. CardioOncology · 2026Article
- Ge11-Modified pH-Sensitive Polymer Micelles: A New Breakthrough in Targeted Therapy for Non-Small-Cell Lung Cancer.Pharmaceutics · 2026Article
- Functional Genomics Illuminates Mechanisms of Anthracycline Cardiotoxicity.JACC. CardioOncology · 2026Article
- CRISPRi/a screens in human iPSC-cardiomyocytes identify glycolytic activation as a druggable target for doxorubicin-induced cardiotoxicity.Cell stem cell · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDoxorubicin (DOX) causes cardiotoxicity and heart failure in a significant fraction of patients, but the molecular etiology is poorly understood.
objectivesWe adopted a functional genomics-based approach to probe the genetic basis for DOX-induced cardiotoxicity in an exhaustive and agnostic manner.
methodsGenome-wide and targeted CRISPR/Cas9 screens were performed in immortalized cardiomyocytes and induced pluripotent stem cell-derived cardiomyocytes to identify genetic modifiers of DOX-induced cardiotoxicity.
resultsOur first screen revealed that loss of the Retinoic Acid Receptor Alpha gene (RARA) increased DOX-induced cell death. Conversely, pharmacological activation of RARA protein with tamibarotene reduced DOX-induced toxicity. RNA-Seq analysis showed that whereas DOX broadly suppressed expression of metabolic and mitochondrial genes, tamibarotene mitigated this effect. In a second screen, we interrogated processes involved in DOX uptake, transport, and efflux. Loss of lysosome homeostasis, exemplified by SPNS lysolipid transporter 1 (SPNS1) deficiency, led to DOX hyperaccumulation, suppression of autophagy, increased DNA damage, and increased cell death. In contrast, ribosome loss-of-function and nutrient deprivation significantly reduced DOX accumulation and toxicity.
conclusionsOur study identified numerous drug-gene interactions that illuminate mechanisms underlying DOX-induced cardiotoxicity and provide a technical framework for future functional genomics screens to nominate therapeutic targets and genetic biomarkers.
Indexed as
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.