ArticleCancer science2013
Identification of a lung adenocarcinoma cell line with CCDC6-RET fusion gene and the effect of RET inhibitors in vitro and in vivo.
Article in Cancer science, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 67 citations in OpenAlex.
- An integrative pan cancer analysis of RET aberrations and their potential clinical implications.Scientific reports · 2022Article
- Article
- Circular RNA circDNA2 upregulatesMolecular therapy. Nucleic acids · 2021Article
- Computational analysis of sense-antisense chimeric transcripts reveals their potential regulatory features and the landscape of expression in human cells.NAR genomics and bioinformatics · 2021Article
- [Research Progress of Fusion Genes RET in Non-small Cell Lung Cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2021Review
- De novo deoxyribonucleotide biosynthesis regulates cell growth and tumor progression in small-cell lung carcinoma.Scientific reports · 2021Article
- Review
- Overcoming TKI resistance in fusion-driven NSCLC: new generation inhibitors and rationale for combination strategies.Translational lung cancer research · 2020Review
- The clinical significance of RET gene fusion among Chinese patients with lung cancer.Translational cancer research · 2020Article
- Long-read sequencing for non-small-cell lung cancer genomes.Genome research · 2020Article
- Bioisosteric Discovery of NPA101.3, a Second-Generation RET/VEGFR2 Inhibitor Optimized for Single-Agent Polypharmacology.Journal of medicinal chemistry · 2020Article
- Article
- Simultaneous Detection of the T790M and L858R Mutations in theInternational journal of molecular sciences · 2019Article
- Liquid biopsy for lung cancers: an update on recent developments.Annals of translational medicine · 2019Review
- Expression of C-terminal ALK, RET, or ROS1 in lung cancer cells with or without fusion.BMC cancer · 2019Article
- CCDC6, a gene product in fusion with different protoncogenes, as a potential chemotherapeutic target.Cancer biomarkers : section A of Disease markers · 2019Review
- Targeting RET-driven cancers: lessons from evolving preclinical and clinical landscapes.Nature reviews. Clinical oncology · 2018Review
- Triple Angiokinase Inhibitor Nintedanib Directly Inhibits Tumor Cell Growth and Induces Tumor Shrinkage via Blocking Oncogenic Receptor Tyrosine Kinases.The Journal of pharmacology and experimental therapeutics · 2018Article
- Inhibitor repurposing reveals ALK, LTK, FGFR, RET and TRK kinases as the targets of AZD1480.Oncotarget · 2017Article
- Sequencing and phasing cancer mutations in lung cancers using a long-read portable sequencer.DNA research : an international journal for rapid publication of reports on genes and genomes · 2017Article
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Rearrangements of the proto-oncogene RET are newly identified potential driver mutations in lung adenocarcinoma (LAD). However, the absence of cell lines harboring RET fusion genes has hampered the investigation of the biological relevance of RET and the development of RET-targeted therapy. Thus, we aimed to identify a RET fusion positive LAD cell line. Eleven LAD cell lines were screened for RET fusion transcripts by reverse transcription-polymerase chain reaction. The biological relevance of the CCDC6-RET gene products was assessed by cell growth, survival and phosphorylation of ERK1/2 and AKT with or without the suppression of RET expression using RNA interference. The efficacy of RET inhibitors was evaluated in vitro using a culture system and in an in vivo xenograft model. Expression of the CCDC6-RET fusion gene in LC-2/ad cells was demonstrated by the mRNA and protein levels, and the genomic break-point was confirmed by genomic DNA sequencing. Mutations in KRAS and EGFR were not observed in the LC-2/ad cells. CCDC6-RET was constitutively active, and the introduction of a siRNA targeting the RET 3' region decreased cell proliferation by downregulating RET and ERK1/2 phosphorylation. Moreover, treatment with RET-inhibitors, including vandetanib, reduced cell viability, which was accompanied by the downregulation of the AKT and ERK1/2 signaling pathways. Vandetanib exhibited anti-tumor effects in the xenograft model. Endogenously expressing CCDC6-RET contributed to cell growth. The inhibition of kinase activity could be an effective treatment strategy for LAD. LC-2/ad is a useful model for developing fusion RET-targeted therapy.
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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.