Synthetic lethal interaction of CDK inhibition and autophagy inhibition in human solid cancer cell lines

2014 Fiscal Year Final Research Report

• Project/Area Number: 24501349
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Clinical oncology
• Research Institution: Juntendo University (2013-2014); Tohoku University (2012)
• Principal Investigator: SHUNSUKE Kato 順天堂大学, 医学(系)研究科(研究院), 教授 (40312657)
• Co-Investigator(Kenkyū-buntansha): KAKUDO Yuichi 東北大学, 加齢医学研究所, 助教 (10396484)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: オートファジー / CDK阻害剤 / 分子標的治療 / 大腸がん

Outline of Final Research Achievements

We revealed that CDK inhibitor induced autophagy in some, but not all, solid cancer cell lines. In the cell lines showing autophagy, which was induced by CDK inhibitor, the combination of CDK inhibitor and autophagy inhibition induced apoptosis. However, it did not induce apoptosis in the cell lines in which autophagy was not induced by CDK inhibitor. These findings indicate that the autophagy induced by CDK inhibitor mimics stress-induced autophagy in some solid cancer cell lines. The combination of a small-molecule CDK inhibitor involved in G1/S arrest and an autophagy inhibitor leads to a synthetic lethal interaction and could become a new antitumor strategy for solid tumors showing cytoprotective autophagy induced by small-molecule CDK inhibitors.

Free Research Field

臨床腫瘍学