A treatment strategy targeting ERBB2 to overcome chemoradiation resistance in muscle-invasive bladder cancer
Project/Area Number |
26860983
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Radiation science
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Research Institution | Tokyo Medical and Dental University |
Principal Investigator |
INOUE Masaharu 東京医科歯科大学, 医学部附属病院, 助教 (30727235)
|
Project Period (FY) |
2014-04-01 – 2017-03-31
|
Project Status |
Completed (Fiscal Year 2016)
|
Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2014: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
|
Keywords | 膀胱癌 / 化学放射線療法 / ERBB2 / 筋層浸潤膀胱癌 / 治療耐性 / 浸潤性膀胱癌 |
Outline of Final Research Achievements |
In this study, we aimed to develop a treatment strategy targeting ERBB2 to overcome chemoradiation (CRT) resistance in muscle-invasive bladder cancer (MIBC). We evaluated ERBB2 expression in MIBC patients treated with CRT and demonstrated that ERBB2 overexpression was associated with CRT resistance and unfavorable cancer-specific survival. A ERBB2 inhibitor trastuzumab and a HSP90 inhibitor ganetespib showed inhibition of proliferation in bladder cancer cell lines (UMUC3, T24 and 5637), inactivating ERBB2. In mice UMUC3 tumor xenografts model, ganetespib combined with radiotherapy more effectively inhibited tumor growth than ganetespib or radiotherapy alone did. Our results suggest ERBB2 and HSP90 could be the targets to improve the outcomes of MIBC patients treated with CRT.
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Report
(4 results)
Research Products
(13 results)
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[Journal Article] Potential Utility of Diffusion-Weighted Magnetic Resonance Imaging in Diagnosis of Residual Bladder Cancer before Second Transurethral Resection.2017
Author(s)
Nakamura Y, Yoshida S, Tanaka H, Inoue M, Ito M, Kijima T, Yokoyama M, Ishioka J, Matsuoka Y, Saito K, Fujii Y, Kihara K.
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Journal Title
Urol Int.
Volume: 98
Issue: 3
Pages: 298-303
DOI
Related Report
Peer Reviewed
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[Journal Article] High Ki-67 Expression Predicts Favorable Survival in Muscle-Invasive Bladder Cancer Patients Treated With Chemoradiation-Based Bladder-Sparing Protocol.2015
Author(s)
Tanabe K, Yoshida S, Koga F, Inoue M, Kobayashi S, Ishioka J, Tamura T, Sugawara E, Saito K, Akashi T, Fujii Y, Kihara K.
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Journal Title
Clin Genitourin Cancer.
Volume: 13
Issue: 4
Pages: e243-e251
DOI
Related Report
Peer Reviewed
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[Presentation] Predictive model for therapeutic resistance using ERBB2 expression status and Ki-67 labeling index in muscle-invasive bladder cancer patients treated with chemoradiotherapy-based bladder-sparing protocol2016
Author(s)
Masaharu Inoue, Fumitaka Koga, Soichiro Yoshida, Hajime Tanaka, Shuichiro Kobayashi, Minato Yokoyama, Junichiro Ishioka, Yoh Matsuoka, Noboru Numao, Kazutaka Saito, Yasuhisa Fujii, Kazunori Kihara,
Organizer
The 112th annual meeting of the American Urological Association
Place of Presentation
San Diego, USA
Year and Date
2016-05-09
Related Report
Int'l Joint Research
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[Presentation] Prediction of therapeutic resistance using ERBB2 expression status and Ki-67 labeling index in muscle-invasive bladder cancer patients treated with chemoradiation-based selective bladder-sparing approach2016
Author(s)
Masaharu Inoue, Fumitaka Koga, Soiciro Yoshida, Hajime Tanaka, Shuichiro Kobayashi, Masaya Ito, Minato Yokoyama, Junichiro Ishioka, Yoh Matsuoka, Noboru Numao, Kazutaka Saito, Yasuhisa Fujii, Kazunori Kihara
Organizer
the 31st Annual EAU Congress
Place of Presentation
Munich, Germany
Year and Date
2016-03-14
Related Report
Int'l Joint Research
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[Presentation] Favorable survival outcomes after a chemoradiation-based multimodal approach against muscle-invasive bladder cancer with high Ki-67 expression2015
Author(s)
Yoshida S., Tanabe K., Koga F., Inoue M., Kobayashi S., Ishioka J., Tamura T., Sugawara E., Saito K., Akashi T., Fujii Y., Kihara K
Organizer
The 111th annual meeting of the American Urological Association
Place of Presentation
New Orleans, USA
Year and Date
2015-05-18
Related Report
Int'l Joint Research
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[Presentation] Optimal MRI-targeted biopsy sampling number2015
Author(s)
Numao N., Ito M., Uchida Y., Yoshida S., Nakayama T., Inoue M., Tatokoro M., Yokoyama M., Ishioka J., Matsuoka Y., Saito K., Fujii Y., Kihara K
Organizer
The 111th annual meeting of the American Urological Association
Place of Presentation
New Orleans, USA
Year and Date
2015-05-17
Related Report
Int'l Joint Research
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[Presentation] Progression of hypertension after partial nephrectomy in Japanese patients with renal tumors2015
Author(s)
Masaharu Inoue, Yasuhisa Fujii, Minato Yokoyama, Masaya Ito, Manabu Tatokoro, Soichiro Yoshida, Junichiro Ishioka, Yoh Matsuoka, Noboru Numao, Kazutaka Saito, Kazunori Kihara
Organizer
the 30th Annual EAU Congress
Place of Presentation
Madrid, Spain
Year and Date
2015-03-21
Related Report
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[Presentation] ErbB2 overexpression is relevant to therapeutic resistance and poor prognosis in muscle-invasive bladder cancer patients treated with chemoradiation-based bladder-sparing protocol2014
Author(s)
Masaharu Inoue, Fumitaka Koga, Soichiro Yoshida, Toshiki Kijima, Yasukazu Nakanishi, Junichiro Ishioka, Yoh Matsuoka, Noboru Numao, Kazutaka Saito, Yasuhisa Fujii, Kazunori Kihara
Organizer
AUA 2014 annual meeting
Place of Presentation
Orland, USA
Year and Date
2014-05-18
Related Report
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[Presentation] Impact of androgen deprivation therapy on cardiovascular disease in patients with non-metastatic high-risk prostate cancer2014
Author(s)
Masaharu Inoue, Noboru Numao, Masaya Ito, Hideki Takeshita, Toshiki Kijima, Yasukazu Nakanishi, Soichiro Yoshida, Jun-ichiro Ishioka, Yoh Matsuoka, Kazutaka Saito, Yasuhisa Fujii, Kazunori Kihara
Organizer
the 29th Annual EAU Congress
Place of Presentation
Stockholm, Sweden
Year and Date
2014-04-14
Related Report
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[Presentation] ErbB2 overexpression predicts chemoradiotherapy resistance and worse prognosis in muscle-invasive bladder cancer patients treated with induction chemoradiotherapy followed by partial or radical cystectomy2014
Author(s)
Masaharu Inoue, Fumitaka Koga, Soichiro Yoshida, Toshiki Kijima, Yasukazu Nakanishi, Jun-ichiro Ishioka, Yoh Matsuoka, Noboru Numao, Kazutaka Saito, Yasuhisa Fujii, Kazunori Kihara
Organizer
the 29th Annual EAU Congress
Place of Presentation
Stockholm, Sweden
Year and Date
2014-04-13
Related Report