Elucidation of anticancer drug resistance mechanism of lung cancer through FOXM1

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K09175
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55040:Respiratory surgery-related
• Research Institution: Gunma University
• Principal Investigator: Ohtaki Yoichi 群馬大学, 医学部附属病院, 助教 (00625402)
• Co-Investigator(Kenkyū-buntansha): 矢島 俊樹 香川大学, 医学部, 教授 (20346852) ; 横堀 武彦 群馬大学, 未来先端研究機構, 准教授 (60420098) ; 川端 麗香 群馬大学, 未来先端研究機構, 講師 (90721928)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 原発性肺癌 / FOXM1 / 小細胞肺癌

Outline of Final Research Achievements

In this study, we focused on the transcription factor FOXM1 to elucidate the mechanism by which lung cancer cells become resistant to cytotoxic anticancer drugs. FOXM1 expression was upregulated in the resistant lines, and FOXM1 suppression using shRNA improved sensitivity to cytotoxic anticancer drugs. Since previous data have shown that FOXM1 expression is higher in small cell lung cancer (SCLC) than in non-small cell lung cancer, we focused on the relationship between SCLC and FOXM1 expression. FOXM1 expression was significantly higher in NeuroD1 type cell lines of high-grade neuroendocrine carcinoma (SCLC+LCNEC). FOXM1 expression was also high in specimens with high neuroendocrine characteristics, such as ASCL1 and NeuroD1.
Thus, FOXM1 is involved in the resistance to cytotoxic anticancer drugs and may be especially effective in tumors with high neuroendocrine characteristics such as ASCL1 and NeuroD1 in HGNECs.

Free Research Field

呼吸器悪性腫瘍

Academic Significance and Societal Importance of the Research Achievements

本研究の結果により、FOXM1は殺細胞性抗がん剤の耐性に寄与しており、FOXM1の阻害によって抗がん剤耐性を改善できる可能性が示された。肺癌の中で、特に新規治療法の開発が遅れている高悪性度神経内分泌癌での治療標的としてのFOXM1の有用性が明らかとなった。本研究は高悪性度神経内分泌癌に対する新規標的治療の基礎的データとして価値をもつものと考えられた。