ArticleClinical cancer research : an official journal of the American Association for Cancer Research2012
Targeted inhibition of Src kinase with dasatinib blocks thyroid cancer growth and metastasis.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers, 1 of them a synthesis that pooled it.
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Who cites it
68 citing papers in PubMed, 1 synthesis or guideline pooled it, 114 citations in OpenAlex.
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- BCL2L11 Induction Mediates Sensitivity to Src and MEK1/2 Inhibition in Thyroid Cancer.Cancers · 2023Article
- Immune Pathways with Aging Characteristics Improve Immunotherapy Benefits and Drug Prediction in Human Cancer.Cancers · 2023Article
- Cuproptosis-related lncRNAs predict prognosis and immune response of thyroid carcinoma.Frontiers in genetics · 2023Article
- Reduction in Lens Epithelial Cell Senescence Burden through Dasatinib Plus Quercetin or Rapamycin Alleviates D-Galactose-Induced Cataract Progression.Journal of functional biomaterials · 2022Article
- A Phase I Study of the Non-Receptor Kinase Inhibitor Bosutinib in Combination with Pemetrexed in Patients with Selected Metastatic Solid Tumors.Current oncology (Toronto, Ont.) · 2022Article
- Integrative and Comprehensive Pan-Cancer Analysis of Lymphocyte-Specific Protein Tyrosine Kinase in Human Tumors.International journal of molecular sciences · 2022Article
8 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
purposeThere are no effective therapies for patients with poorly differentiated papillary thyroid cancer (PTC) or anaplastic thyroid cancer (ATC), and metastasis to the bone represents a significantly worse prognosis. Src family kinases (SFKs) are overexpressed and activated in numerous tumor types and have emerged as a promising therapeutic target, especially in relation to metastasis. We recently showed that Src is overexpressed and activated in thyroid cancer. We therefore tested whether inhibition of Src with dasatinib (BMS-354825) blocks thyroid cancer growth and metastasis. EXPERIMENTAL
designThe effects of dasatinib on thyroid cancer growth, signaling, cell cycle, and apoptosis were evaluated in vitro. The therapeutic efficacy of dasatinib was further tested in vivo using an orthotopic and a novel experimental metastasis model. Expression and activation of SFKs in thyroid cancer cells was characterized, and selectivity of dasatinib was determined using an Src gatekeeper mutant.
resultsDasatinib treatment inhibited Src signaling, decreased growth, and induced cell-cycle arrest and apoptosis in a subset of thyroid cancer cells. Immunoblotting showed that c-Src and Lyn are expressed in thyroid cancer cells and that c-Src is the predominant SFK activated. Treatment with dasatinib blocked PTC tumor growth in an orthotopic model by more than 90% (P = 0.0014). Adjuvant and posttreatment approaches with dasatinib significantly inhibited metastasis (P = 0.016 and P = 0.004, respectively).
conclusionThese data provide the first evidence that Src is a central mediator of thyroid cancer growth and metastasis, indicating that Src inhibitors may have a higher therapeutic efficacy in thyroid cancer, as both antitumor and antimetastatic agents.
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