Discovery of a drug targeting microenvironmental support for lymphoma cells by screening using patient-derived xenograft cells

2014 Fiscal Year Final Research Report

• Project/Area Number: 25670449
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Hematology
• Research Institution: National Hospital Organization Nagoya Medical Center
• Principal Investigator: NAOE TOMOKI 独立行政法人国立病院機構(名古屋医療センター臨床研究センター), その他部局等, 院長 (50217634)
• Co-Investigator(Kenkyū-buntansha): HAYAKAWA Fumihiko 名古屋大学, 医学部附属病院, 講師 (30402580) ; SHIMADA Kazuyuki 名古屋大学, 学内共同利用施設等, 講師 (50631503) ; TOMITA Akihiro 名古屋大学, 医学(系)研究科(研究院), 准教授 (80378215)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: 薬剤スクリーニング / 微小環境 / 悪性リンパ腫 / PDX / 酸化ストレス

Outline of Final Research Achievements

Cell lines have been used for drug discovery as useful models of cancers; however, they do not recapitulate cancers faithfully, especially in the points of rapid growth rate and microenvironment independency. Here, we developed a novel high throughput drug screening system using patient-derived xenograft (PDX) cells of lymphoma that maintained primary cancer cell phenotype more than cell lines. Pyruvinium pamoate showed the highest activity, and its strong anti-tumor effect was confirmed also in vivo. We extensively investigated its mechanism of action and found that it inhibited glutathione supply from stromal cells to lymphoma cells, implying the importance of the stromal protection from oxidative stress for lymphoma cell survival and a new therapeutic strategy for lymphoma. Our system introduces a primary cancer cell phenotype into cell-based phenotype screening and sheds new light on anti-cancer drug development.

Free Research Field

血液内科学