Towards the personalized medicine for metastatic renal cell cancer

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K11035
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Urology
• Research Institution: Japanese Foundation for Cancer Research
• Principal Investigator: YUASA Takeshi 公益財団法人がん研究会, 有明病院 泌尿器科, 副部長 (00314162)
• Research Collaborator: YONESE junichi ; ISHIKAWA yuichi ; ISONO takahiro
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 腎癌 / 分子標的治療 / 予後因子

Outline of Final Research Achievements

One of the most important efficacies of angiogenesis inhibitors is glucose deprivation for RCC cells. We investigated the mechanism of resistance against glucose deprivation of cancer cell. We found that the resistant type possessed higher activities for both mitochondrial oxidative phosphorylation and glycolysis than the sensitive types. These higher activities were supported by the stored carbon, lipid and carbohydrate sources, and by a low level of mitochondrial ROS due to sustained SOD2 expression in the resistant RCC cells. Next, deprivation-resistant RCC, that had lost von Hippel-Lindau (VHL) tumor suppressor expression, expressed hydroxyl-HIF2-alpha in the nucleus, but not sensitive- RCCs. Hydroxyl-HIF2-alpha might be a potential therapeutic target for RCCs. At last, by global transcriptome analysis, ARL4C was shown to be a predictive biomarker for poor prognosis in patients with RCC and may be a novel target in the treatment of RCC.

Free Research Field

泌尿器腫瘍学

Academic Significance and Societal Importance of the Research Achievements

転移性腎細胞癌に対して、血管新生阻害剤治療時においてHIF-2(hypoxia inducible factor)シグナルによる治療耐性をあきらかにし、新規の予後不良遺伝子ADP-ribosylation factor-like 4Cを同定することによって将来的に新たな治療戦略の基礎になる可能性がある。さらにInternational Metastatic renal cell cancer database Consortium (IMDC)国際共同研究は後方視的研究ではあるが、現時点の実臨床における様々な問題点を解決するヒントになっていると思う。