Development of VHL-targeted therapy in malignant pleural mesothelioma

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K06878
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor therapeutics
• Research Institution: Wakayama Medical University
• Principal Investigator: Koh Yasuhiro 和歌山県立医科大学, 医学部, 准教授 (80426519)
• Co-Investigator(Renkei-kenkyūsha): KIKUCHI Takashi 和歌山県立医科大学, 医学部, 助教 (40649050)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 悪性胸膜中皮腫 / VHL変異 / がん個別化医療

Outline of Final Research Achievements

We previously reported on VHL mutations in malignant pleural mesothelioma (MPM) patients’ samples. Here we conduct in vitro study to access the therapeutic approaches in VHL-mutant MPM. MPM cell lines with or without VHL mutation were used in this study. Molecular targeted agents were tested for growth-inhibitory effect and the effects of HIF-1α knockdown by siRNA were also evaluated in these cell lines.
NCI-H28 MPM cells harboring VHL L89H mutation were sensitive to YC-1, known as a hypoxia inducible factor (HIF)-1α inhibitor, and YC-1 treatment induced massive apoptosis. YC-1 had no effect in the other MPM cells without VHL mutations. Knockdown of HIF-1α by siRNA partially inhibited the growth of NCI-H28 cells, suggesting additional blockade may be required for complete shutdown of growth signaling. Further investigation is necessary to detect other molecules relevant to VHL-HIF pathway for the development of better therapeutic approaches.

Free Research Field

腫瘍生物学