Development of nestin-based therapeutic strategy for overcoming anticancer drug resistance in small cell lung cancer

• Project/Area Number: 18K08181
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Nagoya City University
• Principal Investigator: Maeno Ken 名古屋市立大学, 医薬学総合研究院(医学), 准教授 (10444952)
• Co-Investigator(Kenkyū-buntansha): 小栗 鉄也 名古屋市立大学, 医薬学総合研究院(医学), 教授 (60363925)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: ネスチン / 小細胞肺癌 / 抗癌剤耐性

Outline of Final Research Achievements

Aiming to establish a new treatment strategy for small cell lung cancer, we verified the significance of nestin, a neural stem cell marker. We measured plasma nestin concentrations before and after treatment in patients with small cell lung cancer and examined their relationship with clinical parameters. We divided the patients into two groups, high and low, according to the plasma nestin concentration before treatment, and found that among the patients who received combined treatment with anticancer drugs and immune checkpoint inhibitors, the high group had significantly shorter progression-free survival than the low group. This may be due to the tumor microenvironment being more immune evasive in the high group than in the low group.

Academic Significance and Societal Importance of the Research Achievements

小細胞肺癌は生命予後不良な難治性の疾患であり、治療成績の向上は喫緊の課題である。2019年に抗癌剤と免疫チェックポイント阻害薬の併用が標準治療となるも、患者全体としての効果は限定的であり、効果予測バイオマーカーの同定が強く望まれている。本研究成果はその同定に繋がり得るものであり、学術的意義は高い。また、小細胞肺癌の実臨床において十分量の腫瘍組織検体の採取は難しいため、血液検体を用いた本研究は低侵襲性の観点からも臨床的有用性が高い。

Research Products

• [Journal Article] Nestin Expression Affects Resistance to Chemotherapy and Clinical Outcome in Small Cell Lung Cancer (2020)
  • Author(s): Sone Kazuki、Maeno Ken、Masaki Ayako、Kunii Eiji、Takakuwa Osamu、Kagawa Yusuke、Takeuchi Akira、Fukuda Satoshi、Uemura Takehiro、Fukumitsu Kensuke、Kanemitsu Yoshihiro、Ohkubo Hirotsugu、Takemura Masaya、Ito Yutaka、Oguri Tetsuya、Inagaki Hiroshi、Niimi Akio
  • Journal Title: Frontiers in Oncology Volume: 10 Pages: 1367-1367
  • DOI: 10.3389/fonc.2020.01367
  • Peer Reviewed / Open Access
• [Presentation] Expression of nestin affect resistance to chemotherapy and clinical outcome in small cell lung cancer (2018)
  • Author(s): Sone K, Maeno K, Kunii E, Takakuwa O, Takeuchi A, Fukuda S, Asano T, Kanemitsu Y, Ohkubo H, Takemura M, Ito Y, Oguri T, Niimi A
  • Organizer: American Association of Cancer Research Annual Meeting
  • Int'l Joint Research