Analysis of cancer relapse mechanisms by proteomic profiling using drug-tolerant cell subpopulation

2014 Fiscal Year Final Research Report

• Project/Area Number: 25830121
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor therapeutics
• Research Institution: Iwate Medical University
• Principal Investigator: KUME Kohei 岩手医科大学, 医学部, ポストドクター (10609663)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: 抗癌剤耐性 / 癌性腹膜炎 / RNAポリメラーゼ / 逆相タンパク質マイクロアレイ / 逆相タンパク質マイクロアレイ

Outline of Final Research Achievements

Cancer relapse is often seen even after curative operation followed by adjuvant chemotherapy. In this study, we analyzed cancer cell colonies that emerge in the presence of anticancer drugs (drug-tolerant colonies, DTCs) as a cancer relapse model. Proteomic characterization of DTCs identified two major subgroups, but none of these characters associated with DTCs. A lead compound screening identified an RNA polymerase inhibitor (RNAPi) bearing potency in DTC suppression. RNAPi with cisplatin significantly reduced the number of nodules of peritoneal dissemination of gastric cancer in mice. These findings suggest that RNAPi is potent in suppression of cancer relapse such as peritoneal dissemination of gastric cancer.

Free Research Field

癌の分子細胞生物学