ArticleCancer research2016
Multikinase Inhibitors Induce Cutaneous Toxicity through OAT6-Mediated Uptake and MAP3K7-Driven Cell Death.
Article in Cancer research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 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
28 citing papers in PubMed, 46 citations in OpenAlex.
- MAP3K7 is recurrently deleted in pediatric T-lymphoblastic leukemia and affects cell proliferation independently of NF-κB.BMC cancer · 2018Trial
- Transforming a Roadblock into a Roadmap: Evolving HFSR Management From Adverse Event to Efficacy Biomarker.Current treatment options in oncology · 2026Review
- Role of solute carrier transporters in the biodistribution and toxicity of chemotherapeutic drugs.Pharmacological reviews · 2026Review
- Hand-foot skin reaction associated with vascular endothelial growth factor receptor tyrosine kinase inhibitors: a FAERS-based pharmacovigilance study.Frontiers in medicine · 2026Article
- Dual inhibition of IRAK1/TAK1 signaling in astrocytes reduces accelerated mortality in human APOE4 knock-in APPswe/PSEN1dE9/P301S-Tau triple transgenic mouse model.Journal of neuroinflammation · 2025Article
- AR loss in prostate cancer stroma mediated by NF-κB and p38-MAPK signaling disrupts stromal morphogen production.Oncogene · 2024Article
- Review
- Safety profile of vascular endothelial growth factor receptor tyrosine-kinase inhibitors in pediatrics: a pharmacovigilance disproportionality analysis.Frontiers in pharmacology · 2023Article
- Evaluation of Antineoplastic Delayed-Type Hypersensitivity Skin Reactions In Vitro.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Solute Carrier Transportome in Chemotherapy-Induced Adverse Drug Reactions.Reviews of physiology, biochemistry and pharmacology · 2022Article
- Apatinib-Induced Hand-Foot Skin Reaction in Chinese Patients With Liver Cancer.Frontiers in oncology · 2021Review
- Solute transporters and malignancy: establishing the role of uptake transporters in breast cancer and breast cancer metastasis.Cancer metastasis reviews · 2020Review
- Influence of Probenecid on the Pharmacokinetics and Pharmacodynamics of Sorafenib.Pharmaceutics · 2020Article
- Low-Dose Sorafenib Acts as a Mitochondrial Uncoupler and Ameliorates Nonalcoholic Steatohepatitis.Cell metabolism · 2020Article
- Repurposing Tyrosine Kinase Inhibitors to Overcome Multidrug Resistance in Cancer: A Focus on Transporters and Lysosomal Sequestration.International journal of molecular sciences · 2020Review
- Article
- Sorafenib Population Pharmacokinetics and Skin Toxicities in Children and Adolescents with Refractory/Relapsed Leukemia or Solid Tumor Malignancies.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- Targeted Therapy for Advanced Thyroid Cancer: Kinase Inhibitors and Beyond.Endocrine reviews · 2019Review
- Clinically relevant drug interactions with multikinase inhibitors: a review.Therapeutic advances in medical oncology · 2019Review
- Genetic Heterogeneity of SLC22 Family of Transporters in Drug Disposition.Journal of personalized medicine · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
The use of multikinase inhibitors (MKI) in oncology, such as sorafenib, is associated with a cutaneous adverse event called hand-foot skin reaction (HFSR), in which sites of pressure or friction become inflamed and painful, thus significantly impacting quality of life. The pathogenesis of MKI-induced HFSR is unknown, and the only available treatment options involve dose reduction or discontinuation of therapy, which have negative effects on primary disease management. To investigate the underlying mechanisms by which sorafenib promotes keratinocyte cytotoxicity and subsequent HFSR induction, we performed a transporter-directed RNAi screen in human epidermal keratinocytes and identified SLC22A20 (OAT6) as an uptake carrier of sorafenib. Further investigations into the intracellular mechanism of sorafenib activity through in situ kinome profiling identified the mitogen-activated protein kinase MAP3K7 (TAK1) as a target of sorafenib that induces cell death. Finally, we demonstrate that sorafenib induced keratinocyte injury in vivo and that this effect could be reversed by cotreatment with the OAT6 inhibitor probenecid. Collectively, our findings reveal a novel pathway that regulates the entry of some MKIs into keratinocytes and explains the basis underlying sorafenib-induced skin toxicity, with important implications for the therapeutic management of HFSR.
Indexed as
Identifiers
What OpenQuestion 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 OpenQuestion graph.