Combined inhibition of stem cell markers and histone modification enzymes in non-small cell lung cancer

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461175
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Hokkaido University
• Principal Investigator: Kinoshita Ichiro 北海道大学, 医学研究科, 准教授 (40343008)
• Co-Investigator(Renkei-kenkyūsha): JINUSHI Masahisa 慶應義塾大学, 医学部, 特任准教授 (40318085) ; AKITA Hirotoshi 北海道大学, 医学研究科, 教授 (70222528)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 肺癌 / ヒストン修飾 / 癌幹細胞 / EZH2 / DZNep / HDAC / SAHA / side population

Outline of Final Research Achievements

EGFR-tyrosine kinase inhibitor (TKI) resistant non-small lung cancer (NSCLC) cell H1975 had 1% side population fraction, which showed increased tumorigenicity, elevated expression of stem cell markers and histone H3K27 trimethyl transferase EZH2, suggesting that EZH2 may play a role in maintenance of cancer stem cells. The combined treatment with inhibitors of the EZH2 and the histone deacetylases HDACs showed synergistic growth suppressive effects, suppression of EGFR signaling, and decrease in the in vivo tumor growth of H1975 cells, suggesting that the combined pharmacological targeting of the histone modification enzymes may provide more effective epigenetic therapeutics for NSCLCs including those with EGFR-TKI-resistant mutations.

Free Research Field

腫瘍内科学