ArticleOncotarget2016
Dasatinib induces DNA damage and activates DNA repair pathways leading to senescence in non-small cell lung cancer cell lines with kinase-inactivating BRAF mutations.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 38 citations in OpenAlex.
- Design, synthesis, andRSC medicinal chemistry · 2026Article
- Disproportionality Analysis of Hematologic Adverse Event Signals Associated with Venetoclax in Combination with Senescence-Inducing Chemotherapy.Journal of clinical medicine · 2026Article
- The controversial role of senescence-associated secretory phenotype (SASP) in cancer therapy.Molecular cancer · 2025Review
- 3D models to study therapy-induced senescence: where do we stand now?Cytotechnology · 2025Review
- The Emerging Role of p21 in Diabetes and Related Metabolic Disorders.International journal of molecular sciences · 2024Review
- Association of changes in expression ofEpigenetics · 2024Article
- Integration of transcriptomics, proteomics and loss-of-function screening reveals WEE1 as a target for combination with dasatinib against proneural glioblastoma.Cancer letters · 2024Article
- Adverse Toxic Effects of Tyrosine Kinase Inhibitors on Non-Target Zebrafish Liver (ZFL) Cells.International journal of molecular sciences · 2023Article
- Combined PARP inhibitors and small molecular inhibitors in solid tumor treatment (Review).International journal of oncology · 2023Review
- Interplay of Developmental Hippo-Notch Signaling Pathways with the DNA Damage Response in Prostate Cancer.Cells · 2022Review
- Targeting the FAK-Src Complex in Desmoplastic Small Round Cell Tumors, Ewing Sarcoma, and Rhabdomyosarcoma.Sarcoma · 2022Article
- The Radiosensitizing Effect of AZD0530 in Glioblastoma and Glioblastoma Stem-Like Cells.Molecular cancer therapeutics · 2021Article
- Transcriptomic Changes Associated with Loss of Cell Viability Induced by Oxysterol Treatment of a Retinal Photoreceptor-Derived Cell Line: An In Vitro Model of Smith-Lemli-Opitz Syndrome.International journal of molecular sciences · 2021Article
- Review
- Mechanisms of Hydroxyurea-Induced Cellular Senescence: An Oxidative Stress Connection?Oxidative medicine and cellular longevity · 2021Review
- Review
- Hippo Pathway and YAP Signaling Alterations in Squamous Cancer of the Head and Neck.Journal of clinical medicine · 2019Review
- Inhibition of lung cancer cells and Ras/Raf/MEK/ERK signal transduction by ectonucleoside triphosphate phosphohydrolase-7 (ENTPD7).Respiratory research · 2019Article
- Non-canonical cMet regulation by vimentin mediates Plk1 inhibitor-induced apoptosis.EMBO molecular medicine · 2019Article
- Phase I study of the combination of crizotinib (as a MET inhibitor) and dasatinib (as a c-SRC inhibitor) in patients with advanced cancer.Investigational new drugs · 2018Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Improved therapies are greatly needed for non-small cell lung cancer (NSCLC) that does not harbor targetable kinase mutations or translocations. We previously demonstrated that NSCLC cells that harbor kinase-inactivating BRAF mutations (KIBRAF) undergo senescence when treated with the multitargeted kinase inhibitor dasatinib. Similarly, treatment with dasatinib resulted in a profound and durable response in a patient with KIBRAF NSCLC. However, no canonical pathways explain dasatinib-induced senescence in KIBRAF NSCLC. To investigate the underlying mechanism, we used 2 approaches: gene expression and reverse phase protein arrays. Both approaches showed that DNA repair pathways were differentially modulated between KIBRAF NSCLC cells and those with wild-type (WT) BRAF. Consistent with these findings, dasatinib induced DNA damage and activated DNA repair pathways leading to senescence only in the KIBRAF cells. Moreover, dasatinib-induced senescence was dependent on Chk1 and p21, proteins known to mediate DNA damage-induced senescence. Dasatinib also led to a marked decrease in TAZ but not YAP protein levels. Overexpression of TAZ inhibited dasatinib-induced senescence. To investigate other vulnerabilities in KIBRAF NSCLC cells, we compared the sensitivity of these cells with that of WTBRAF NSCLC cells to 79 drugs and identified a pattern of sensitivity to EGFR and MEK inhibitors in the KIBRAF cells. Clinically approved EGFR and MEK inhibitors, which are better tolerated than dasatinib, could be used to treat KIBRAF NSCLC. Our novel finding that dasatinib induced DNA damage and subsequently activated DNA repair pathways leading to senescence in KIBRAF NSCLC cells represents a unique vulnerability with potential clinical applications.
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