| Sunitinib inhibits papillary thyroid carcinoma with RET/PTC rearrangement but not BRAF mutation. | |
| | |
MedLine Citation:
|
PMID: 21725210 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Sunitinib, a multi-targeted tyrosine kinase inhibitor, is frequently incorporated into the management of papillary thyroid carcinoma refractory to standard therapies. Although clinical trials are in progress, the mechanism of action in papillary thyroid carcinomas is not clear, especially regarding the effect on BRAF mutation. We investigated the effect of sunitinib on papillary thyroid carcinoma cells harboring RET/PTC rearrangement and BRAF mutation using TPC-1M, SNU-790, and B-cPAP cell lines. Cell growth of papillary thyroid cancer cells with RET/PTC rearrangement was effectively inhibited at low doses of sunitinib (IC50=0.658 μM), whereas that of BRAF mutated cells required higher doses. Immunoblotting revealed effective blocking of MEK/ERK pathway in RET/PTC rearrangement cells, but not in BRAF mutated cells. Cell cycle analysis showed G1 arrest in RET/PTC rearrangement cells. In vivo orthotopic thyroid cancer mouse model demonstrated statistically significant tumor growth inhibition by sunitinib in RET/PTC rearrangement cancer cells. We conclude that sunitinib effectively inhibits RET/PTC rearrangement cells but not BRAF mutated cells. These data suggest that sunitinib exerts its effect by inhibiting the upstream MAPK signaling cascade. These findings support the unsatisfactory treatment outcomes of sunitinib in many already ongoing clinical trials compared to other tyrosine kinase inhibitors. Clinical application of sunitinib should be directed accordingly. |
| | |
Authors:
|
Woo-Jin Jeong; Ji-Hun Mo; Min Woo Park; Ik Joon Choi; Soo-Youn An; Eun-Hee Jeon; Soon-Hyun Ahn |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2011-09-01 |
Journal Detail:
|
Title: Cancer biology & therapy Volume: 12 ISSN: 1555-8576 ISO Abbreviation: Cancer Biol. Ther. Publication Date: 2011 Sep |
Date Detail:
|
Created Date: 2011-09-02 Completed Date: 2012-01-26 Revised Date: 2012-06-21 |
Medline Journal Info:
|
Nlm Unique ID: 101137842 Medline TA: Cancer Biol Ther Country: United States |
Other Details:
|
Languages: eng Pagination: 458-65 Citation Subset: IM |
Affiliation:
|
Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Cell Cycle / drug effects Cell Line, Tumor Cell Proliferation / drug effects DNA-Binding Proteins / genetics* Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors Humans Indoles / pharmacology* MAP Kinase Kinase Kinases / antagonists & inhibitors Mice Mutation Nuclear Proteins / genetics* Proto-Oncogene Proteins B-raf / genetics* Pyrroles / pharmacology* Signal Transduction / drug effects Thyroid Neoplasms / drug therapy*, genetics, prevention & control* Xenograft Model Antitumor Assays raf Kinases / antagonists & inhibitors |
| Chemical | |
Reg. No./Substance:
|
0/DNA-Binding Proteins; 0/Indoles; 0/Nuclear Proteins; 0/Pyrroles; 0/TRIM27 protein, human; 0/sunitinib; EC 2.7.11.1/BRAF protein, human; EC 2.7.11.1/Proto-Oncogene Proteins B-raf; EC 2.7.11.1/raf Kinases; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases; EC 2.7.11.25/MAP Kinase Kinase Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Erlotinib is a viable treatment for tumors with acquired resistance to cetuximab.
Next Document: Vesicle transfer and cell fusion: Emerging concepts of cell-cell communication in the tumor microenv...