A treatment strategy targeting ERBB2 to overcome chemoradiation resistance in muscle-invasive bladder cancer

2016 Fiscal Year Final Research Report

• Project/Area Number: 26860983
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Radiation science
• 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
• Keywords: 膀胱癌 / 化学放射線療法 / ERBB2

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.

Free Research Field

泌尿器科