Back to Search
Start Over
Small molecule inhibitor regorafenib inhibits RET signaling in neuroblastoma cells and effectively suppresses tumor growth in vivo
- Source :
- Oncotarget
- Publication Year :
- 2017
- Publisher :
- Impact Journals LLC, 2017.
-
Abstract
- Neuroblastoma (NB), the most common extracranial pediatric solid tumor, continues to cause significant cancer-related morbidity and mortality in children. Dysregulation of oncogenic receptor tyrosine kinases (RTKs) has been shown to contribute to tumorigenesis in various human cancers and targeting these RTKs has had therapeutic benefit. RET is an RTK which is commonly expressed in NB, and high expression of RET correlates with poor outcomes in patients with NB. Herein we report that RET is required for NB cell proliferation and that the small molecule inhibitor regorafenib (BAY 73-4506) blocks glial cell derived neurotrophic factor (GDNF)-induced RET signaling in NB cells and inhibits NB growth both in vitro and in vivo. We found that regorafenib significantly inhibited cell proliferation and colony formation ability of NB cells. Moreover, regorafenib suppressed tumor growth in both an orthotopic xenograft NB mouse model and a TH-MYCN transgenic NB mouse model. Finally, regorafenib markedly improved the overall survival of TH-MYCN transgenic tumor-bearing mice. In summary, our study suggests that RET is a potential therapeutic target in NB, and that using a novel RET inhibitor, like regorafenib, should be investigated as a therapeutic treatment option for children with NB.
- Subjects :
- 0301 basic medicine
medicine.drug_class
medicine.disease_cause
chemotherapy
Tyrosine-kinase inhibitor
Receptor tyrosine kinase
03 medical and health sciences
chemistry.chemical_compound
neuroblastoma
0302 clinical medicine
tyrosine kinase inhibitor
In vivo
Neuroblastoma
Regorafenib
medicine
Glial cell line-derived neurotrophic factor
neoplasms
biology
Chemistry
Cell growth
medicine.disease
3. Good health
030104 developmental biology
Oncology
030220 oncology & carcinogenesis
biology.protein
Cancer research
regorafenib
Carcinogenesis
RET
Research Paper
Subjects
Details
- Language :
- English
- ISSN :
- 19492553
- Volume :
- 8
- Issue :
- 61
- Database :
- OpenAIRE
- Journal :
- Oncotarget
- Accession number :
- edsair.doi.dedup.....919e965f50fae3f07c61824eb8959e50