Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Drug Toxicity: Risk factors01:24

Drug Toxicity: Risk factors

Adverse Drug Reactions (ADRs) are potential complications that arise during pharmacotherapy, influenced by multiple risk factors. Age plays a significant role; both neonates and the elderly are at heightened risk due to their respective immature and diminished metabolic and elimination processes. Gender also impacts ADRs, with females experiencing a 1.5 to 1.7-fold greater risk than males, which may be linked to pharmacokinetic, pharmacodynamic, and hormonal differences. Notably, neonates, the...
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu01:29

Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu

Genetic variations significantly influence drug response through pharmacokinetics, receptor interactions, and biologic milieu modifications. Pharmacokinetic alterations impact drug metabolism and clearance, affecting efficacy and toxicity. Variants in drug-metabolizing enzymes, such as CYP2C9 and CYP2C19, alter drug activation and elimination. For example, CYP2C9 loss-of-function variants require lower warfarin doses to prevent excessive bleeding, while CYP2C19 variants reduce clopidogrel...
Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers01:26

Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers

Receptor tyrosine kinase inhibitors (TKIs) and calcium channel blockers (CCBs) are two critical categories of drugs employed in the treatment of pulmonary artery hypertension (PAH). PAH is a disease that causes high blood pressure in the pulmonary arteries, resulting in chest pain, fatigue, and shortness of breath.
TKIs, such as imatinib (Gleevec), are particularly effective in tackling the growth and mitogenic factors that become upregulated in PAH patients. These factors contribute to the...
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
Pharmacogenomics: Identification of New Drug Targets01:29

Pharmacogenomics: Identification of New Drug Targets

Advances in genomics have profoundly influenced drug discovery by increasing both the speed and accuracy of pharmaceutical development. Pharmacogenomics, which examines how genetic variation influences drug response, facilitates the identification of novel therapeutic targets and enables patient stratification for personalized treatment. These strategies contribute to improved drug efficacy, minimized adverse effects, and more efficient clinical trial design.Mapping genetic differences...
Therapeutic Drug Monitoring: Affecting Factors01:29

Therapeutic Drug Monitoring: Affecting Factors

Therapeutic Drug Monitoring (TDM) is the clinical practice of measuring specific drug levels in a patient's blood or body tissues to manage and optimize therapy. TDM is crucial for drugs with narrow therapeutic windows, like warfarin and phenytoin, where incorrect doses can lead to treatment failure or severe side effects. This monitoring ensures the dosage administered is within a safe and effective range. The factors affecting therapeutic drug monitoring include:Patient-Specific Factors:a.

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Mapping Physical Fitness Assessments in Interventional Research Among Breast Cancer Survivors: A Scoping Review.

Cancers·2026
Same author

DNA topological regulation by topoisomerase IIβ-DNA-PK interaction is important for controlled hypoxia-inducible gene expression.

bioRxiv : the preprint server for biology·2026
Same author

Identifying Individuals at Risk of Functional Decline Despite Preserved Muscle Mass: Insights from Appendicular Skeletal Muscle Mass and Handgrip Strength Discordance.

Journal of clinical medicine·2026
Same author

Longitudinal Whole-Exome Sequencing Identifies Clonal Hematopoiesis and Genomic Heterogeneity as a Predictor of Treatment Outcome in Patients with Newly Diagnosed, Elderly Chronic Lymphocytic Leukemia.

International journal of molecular sciences·2026
Same author

Irregularity in Daily Activities Predicts Depression via Reduced Perceived Control: A Daily Diary Study.

Journal of clinical psychology·2026
Same author

Preclinical Analysis of Bone Marrow-Derived Stem Cell Therapy Response and Transcriptomic Overlap Analysis in a Severe Alcoholic Hepatitis Mouse Model.

Gut and liver·2026
Same journal

RETRACTED: Kim et al. The Angiogenesis Inhibitor ALS-L1023 from Lemon-Balm Leaves Attenuates High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease Through Regulating the Visceral Adipose-Tissue Function. <i>Int. J. Mol. Sci.</i> 2017, <i>18</i>, 846.

International journal of molecular sciences·2026
Same journal

Correction: Mahmud et al. Thymoquinone Attenuates NF-κβ Signalling Activation in Retinal Pigment Epithelium Cells Under AMD-Mimicking Conditions. <i>Int. J. Mol. Sci.</i> 2025, <i>26</i>, 11473.

International journal of molecular sciences·2026
Same journal

Correction: Borovikov et al. The Twisting and Untwisting of Actin and Tropomyosin Filaments Are Involved in the Molecular Mechanisms of Muscle Contraction, and Their Disruption Can Result in Muscle Disorders. <i>Int. J. Mol. Sci</i>. 2025, <i>26</i>, 6705.

International journal of molecular sciences·2026
Same journal

Correction: Molagoda et al. Flavonoid Glycosides from <i>Ziziphus jujuba</i> var. <i>inermis</i> (Bunge) Rehder Seeds Inhibit α-Melanocyte-Stimulating Hormone-Mediated Melanogenesis. <i>Int. J. Mol. Sci.</i> 2021, <i>22</i>, 7701.

International journal of molecular sciences·2026
Same journal

Correction: Guo et al. Integrated Transcriptomic and Metabolomic Analysis Reveals the Molecular Regulatory Mechanism of Flavonoid Biosynthesis in Maize Roots Under Lead Stress. <i>Int. J. Mol. Sci.</i> 2024, <i>25</i>, 6050.

International journal of molecular sciences·2026
Same journal

Correction: Chang et al. Improvement of Carbon Tetrachloride-Induced Acute Hepatic Failure by Transplantation of Induced Pluripotent Stem Cells Without Reprogramming Factor c-Myc. <i>Int. J. Mol. Sci.</i> 2012, <i>13</i>, 3598-3617.

International journal of molecular sciences·2026
See all related articles

Related Experiment Video

Updated: May 14, 2026

Drug-Induced Senescence in Liver Cells Promotes M2 Macrophage Polarization: Implications for Tyrosine Kinase Inhibitor-Associated Hepatotoxicity
09:32

Drug-Induced Senescence in Liver Cells Promotes M2 Macrophage Polarization: Implications for Tyrosine Kinase Inhibitor-Associated Hepatotoxicity

Published on: October 17, 2025

A Ponatinib-Associated Transcriptomic Signature: Implications for Cardiovascular Toxicity.

Joonho Kong1, Jaeyeon Jang2, Jee Hyun Kong2

  • 1Department of Medicine, Yonsei University Wonju College of Medicine, Wonju 26426, Republic of Korea.

International Journal of Molecular Sciences
|May 13, 2026
PubMed
Summary
This summary is machine-generated.

Ponatinib treatment alters gene expression in cancer cells and cardiomyocytes, revealing a unique transcriptomic signature linked to cardiovascular toxicity. This signature differs from imatinib and highlights key genes for further research.

Keywords:
cardiovascular toxicityiPSC-derived cardiomyocytesmeta-analysisponatinibtranscriptomic signaturetyrosine kinase inhibitor

More Related Videos

High-Throughput Cardiotoxicity Screening Using Mature Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Monolayers
14:03

High-Throughput Cardiotoxicity Screening Using Mature Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Monolayers

Published on: March 24, 2023

Related Experiment Videos

Last Updated: May 14, 2026

Drug-Induced Senescence in Liver Cells Promotes M2 Macrophage Polarization: Implications for Tyrosine Kinase Inhibitor-Associated Hepatotoxicity
09:32

Drug-Induced Senescence in Liver Cells Promotes M2 Macrophage Polarization: Implications for Tyrosine Kinase Inhibitor-Associated Hepatotoxicity

Published on: October 17, 2025

High-Throughput Cardiotoxicity Screening Using Mature Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Monolayers
14:03

High-Throughput Cardiotoxicity Screening Using Mature Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Monolayers

Published on: March 24, 2023

Area of Science:

  • Genomics
  • Cardiovascular Pharmacology
  • Molecular Biology

Background:

  • Ponatinib, a BCR::ABL1 inhibitor, exhibits anti-leukemic effects but poses cardiovascular risks.
  • The precise molecular mechanisms underlying ponatinib-induced cardiotoxicity, particularly at the transcriptome level, require further elucidation.

Purpose of the Study:

  • To define a transcriptomic signature associated with ponatinib treatment.
  • To investigate the mechanistic implications of this signature in cardiovascular toxicity using public RNA sequencing datasets.
  • To identify overlapping gene expression patterns between cancer cell lines and cardiomyocytes treated with ponatinib.

Main Methods:

  • Utilized two RNA sequencing datasets (GSE186341 and GSE217421) comprising cancer cell lines and induced pluripotent stem cell (iPSC)-derived cardiomyocytes.
  • Applied principal component analysis (PCA) and k-means clustering for subgroup identification.
  • Employed DESeq2 and fixed-effect meta-analysis to identify differentially expressed genes (DEGs) and pooled treatment effects.
  • Performed cross-dataset analysis to identify overlapping gene sets between the two datasets.

Main Results:

  • Identified 2639 meta-analytically differentially expressed genes (meta-DEGs) in cancer cell lines.
  • Found 81 overlapping genes differentially expressed in both cancer cell lines and iPSC-derived cardiomyocytes after ponatinib treatment.
  • Observed no overlap in these 81 genes when analyzing imatinib treatment under the same framework.
  • Highlighted cardiotoxicity-relevant genes involved in ion handling, metabolic regulation, stress signaling, and mitochondrial homeostasis.

Conclusions:

  • Defined a distinct ponatinib-associated transcriptomic signature.
  • Nominated specific transcript-level candidates for further investigation into ponatinib-induced cardiotoxicity.
  • Demonstrated the utility of cross-dataset analysis in identifying conserved molecular responses to targeted therapies.