Development of novel therapies targeting the dynamics of tumor microenvironment and HIF-1

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K15589
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52040:Radiological sciences-related
• Research Institution: Kyoto University
• Principal Investigator: Kobayashi Minoru 京都大学, 生命科学研究科, 特定助教 (40644894)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: 低酸素 / 腫瘍内微小環境

Outline of Final Research Achievements

It is known that cancer cells in hypoxic region are radioresistant and contribute to recurrence after radiotherapy. Therefore, the development of therapies that target the tumor microenvironment is desired. However, therapies targeting the tumor microenvironment have yet to be established because of the lack of knowledge about the dynamics of tumor microenvironment.
In order to understand the dynamics of tumor microenvironment, especially the HIF-1 activated cells, we constructed the artificial genes 5HREp-Luc and 5HREp-Cre-ERT2, which labeled and tracked cells in a HIF-1-dependent manner. And we generated these genes knock-in mice from TIGRE locus.
We expect that these mice will be used to get insight into the dynamics of tumor microenvironment.

Free Research Field

放射線腫瘍学

Academic Significance and Societal Importance of the Research Achievements

本研究で作成したTIGRE遺伝子座に5HREp-Lucをknock-inしたマウスを発がんモデルマウスと掛け合わせることで、刻一刻と変化する腫瘍内の低酸素領域とそこに存在するがん細胞を可視化するとともに、さらに現在作成に取り掛かっている5HREp-Cre-ERT2をknock-inしたマウスを用いることで上記した低酸素がん細胞がその後どのような運命を辿るのかを知ることが可能になる。これらのマウスを用いて、抗がん剤治療や放射線治療を行った後の低酸素がん細胞の動態を知ることで、化学放射線療法や放射線多分割照射の効果を最大限に発揮することを可能とする、新たな治療戦略につながることが期待される。