Reference - Detail
| RRC ID | 62250 |
|---|---|
| Author | Shirota T, Ojima H, Hiraoka N, Shimada K, Rokutan H, Arai Y, Kanai Y, Miyagawa S, Shibata T. |
| Title | Heat Shock Protein 90 Is a Potential Therapeutic Target in Cholangiocarcinoma. |
| Journal | Mol Cancer Ther |
| Abstract |
Cholangiocarcinoma is an aggressive malignancy with a poor prognosis, with no effective therapy other than surgical resection. Heat shock protein 90 (HSP90) is a key component of a multichaperone complex involved in the posttranslational folding of a number of client proteins, many of which play essential roles in tumorigenesis. Here, we attempted to clarify its prognostic significance and potential utility as a therapeutic target in cholangiocarcinoma. Immunohistochemical expression of HSP90 was assessed retrospectively in 399 cholangiocarcinoma cases and 17 human cholangiocarcinoma cell lines, along with the effect of a small-molecule HSP90 inhibitor (NVP-AUY922) on cholangiocarcinoma tumor growth and angiogenesis in human cholangiocarcinoma cell lines and xenografts. The positivity of HSP90 was 44.6% in intrahepatic cholangiocarcinoma (IHCC) and 32.8% in extrahepatic cholangiocarcinoma (EHCC), respectively. HSP90 expression was significantly associated with the 5-year survival rate for IHCC (P < 0.001) and EHCC (P < 0.001). HSP90 inhibition showed potent antiproliferative activity and reduced growth-associated signaling in human cholangiocarcinoma cells in vitro. Furthermore, treatment of cholangiocarcinoma xenograft-bearing mice with NVP-AUY922 significantly inhibited growth at doses far below the maximum-tolerated dose. HSP90 overexpression is a prognostic marker for cholangiocarcinoma. HSP90-targeted therapy may be an option for a subset of cholangiocarcinoma. |
| Volume | 14(9) |
| Pages | 1985-93 |
| Published | 2015-9-1 |
| DOI | 10.1158/1535-7163.MCT-15-0069 |
| PII | 1535-7163.MCT-15-0069 |
| PMID | 26141945 |
| MeSH | Adult Aged Aged, 80 and over Animals Antineoplastic Agents / administration & dosage Antineoplastic Agents / pharmacology* Cell Line, Tumor Cholangiocarcinoma / drug therapy Cholangiocarcinoma / metabolism* Cholangiocarcinoma / mortality Cholangiocarcinoma / pathology Cholangiocarcinoma / surgery Disease Models, Animal Female Follow-Up Studies HSP90 Heat-Shock Proteins / antagonists & inhibitors* HSP90 Heat-Shock Proteins / metabolism* Humans Immunohistochemistry Isoxazoles / administration & dosage Isoxazoles / pharmacology Male Mice Middle Aged Molecular Targeted Therapy Neoplasm Staging Prognosis Resorcinols / administration & dosage Resorcinols / pharmacology Treatment Outcome Xenograft Model Antitumor Assays |
| IF | 5.615 |
| Altmetric score |
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 1 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | TKKK(RCB1907) HuCCT1(RCB1960) TGBC24TKB(RCB1196) |