Researching for mechanism of acquired resistance in lung cancer

• Project/Area Number: 18K15961
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Nippon Medical School
• Principal Investigator: SUGANO TEPPEI 日本医科大学, 医学部, 助教 (10809635)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2020: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000); Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 肺癌 / 抗癌剤 / 耐性機序 / 分子標的薬 / 肺がん / 耐性克服 / エクソソーム / がん幹細胞

Outline of Final Research Achievements

Synergistic effects of epidermal growth factor receptor tyrosine kinase inhibitors and chemotherapy have been reported. Here, we evaluated the therapeutic potential of combining osimertinib with pemetrexed and investigated the molecular mechanisms.Blocking PLK1 contributes to mediating the synergistic anti-proliferative effect of osimertinib+pemetrexed. PLK1 over-expression may be a critical mechanism for acquired resistance to osimertinib+pemetrexed.

Academic Significance and Societal Importance of the Research Achievements

肺癌治療は、非常に進歩しており、特にEGFR阻害薬は高い効果をもたらす。我々の研究室では、過去にEGFR阻害薬の耐性機序を明らかにしてきた。また、臨床でEGFR阻害薬と抗癌剤との併用療法が高い効果を認めており、この治療方法に対する耐性機序を明らかにしたことは、肺癌を根治するための一歩として、非常に意味のある研究と考えられる。

Research Products

• [Journal Article] A Novel Molecular Target in EGFR-mutant Lung Cancer Treated With the Combination of Osimertinib and Pemetrexed (2022)
  • Author(s): Natsuki Takano 1, Masahiro Seike 2, Teppei Sugano 1, Kuniko Matsuda 1, Kakeru Hisakane 1, Akiko Yoshikawa 1, Shinji Nakamichi 1, Rintaro Noro 1, Akihiko Gemma 1
  • Journal Title: Anticancer Research Volume: 42 Pages: 709-722
  • Peer Reviewed