ArticleBritish journal of cancer2013
Src kinases in chondrosarcoma chemoresistance and migration: dasatinib sensitises to doxorubicin in TP53 mutant cells.
Article in British journal of cancer, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.
- Mismatch repair deficiency is rare in bone and soft tissue tumors.Histopathology · 2021Pooled it
- Trial
- Chondrosarcoma: A comprehensive review of tumor biology, clinical behavior, and therapeutic advances.Cancer treatment reviews · 2026Review
- The Role of AXL Signaling and MutantCancers · 2026Review
- Proton Irradiation Induces Differential Cellular Responses and Proteomic Signatures in Chondrosarcoma and Chondrocytes.Current issues in molecular biology · 2026Article
- Genetics and Molecular Pathogenesis of the Chondrosarcoma: A Review of the Literature.Current issues in molecular biology · 2024Review
- DNA-PKcs Inhibition Sensitizes Human Chondrosarcoma Cells to Carbon Ion Irradiation via Cell Cycle Arrest and Telomere Capping Disruption.International journal of molecular sciences · 2024Article
- Dual-Multivalent Aptamer-Based Drug Delivery Platform for Targeted SRC Silencing to Enhance Doxorubicin Sensitivity in Endometrial Cancer.International journal of biological sciences · 2024Article
- Dedifferentiated Chondrosarcoma: Diagnostic Controversies and Emerging Therapeutic Targets.Current oncology reports · 2023Review
- Targeting the Src N-terminal regulatory element in cancer.Oncotarget · 2023Article
- A Novel Gemcitabine-Resistant Gallbladder Cancer Model Provides Insights into Molecular Changes Occurring during Acquired Resistance.International journal of molecular sciences · 2023Article
- Chondrosarcoma: A Clinical Review.Journal of clinical medicine · 2023Review
- An overview of resistance to chemotherapy in osteosarcoma and future perspectives.Cancer drug resistance (Alhambra, Calif.) · 2022Review
- Article
- Biological Heterogeneity of Chondrosarcoma: From (Epi) Genetics through Stemness and Deregulated Signaling to Immunophenotype.Cancers · 2021Review
- Metabolic Pathways and Targets in Chondrosarcoma.Frontiers in oncology · 2021Review
- A system-level approach identifies HIF-2α as a critical regulator of chondrosarcoma progression.Nature communications · 2020Article
- Review
- Integrated WGCNA and PPI Network to Screen Hub Genes Signatures for Infantile Hemangioma.Frontiers in genetics · 2020Article
- A screening-based approach identifies cell cycle regulators AURKA, CHK1 and PLK1 as targetable regulators of chondrosarcoma cell survival.Journal of bone oncology · 2019Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundChondrosarcomas are malignant cartilage-forming tumours of bone. Because of their resistance to conventional chemotherapy and radiotherapy, currently no treatment strategies exist for unresectable and metastatic chondrosarcoma. Previously, PI3K/AKT/GSK3β and Src kinase pathways were shown to be activated in chondrosarcoma cell lines. Our aim was to investigate the role of these kinases in chemoresistance and migration in chondrosarcoma in relation to TP53 mutation status.
methodsWe used five conventional and three dedifferentiated chondrosarcoma cell lines and investigated the effect of PI3K/AKT/GSK3β pathway inhibition (enzastaurin) and Src pathway inhibition (dasatinib) in chemoresistance using WST assay and live cell imaging with AnnexinV staining. Immunohistochemistry on tissue microarrays (TMAs) containing 157 cartilaginous tumours was performed for Src family members. Migration assays were performed with the RTCA xCelligence System.
resultsSrc inhibition was found to overcome chemoresistance, to induce apoptosis and to inhibit migration. Cell lines with TP53 mutations responded better to combination therapy than wild-type cell lines (P=0.002). Tissue microarray immunohistochemistry confirmed active Src (pSrc) signalling, with Fyn being most abundantly expressed (76.1%).
conclusionThese results strongly indicate Src family kinases, in particular Fyn, as a potential target for the treatment of inoperable and metastatic chondrosarcomas, and to sensitise for doxorubicin especially in the presence of TP53 mutations.
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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.