HER2 target therapy for multidrug-resistant small cell lung cancer

2014 Fiscal Year Final Research Report

• Project/Area Number: 24591165
• 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: Osaka University
• Principal Investigator: KIJIMA TAKASHI 大阪大学, 医学(系)研究科(研究院), 講師 (90372614)
• Co-Investigator(Kenkyū-buntansha): NAGATOMO Izumi 大阪大学, 大学院医学系研究科, 助教 (10570583) ; KOHMO Satoshi 大阪大学, 大学院医学系研究科, 招聘教員 (40625670) ; MINAMI Toshiyuki 大阪大学, 大学院医学系研究科, 助教 (00705113)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 小細胞肺癌 / 多剤耐性 / 分子標的治療 / HER2 / ラパチニブ / トラスツズマブ

Outline of Final Research Achievements

Small cell lung cancer (SCLC) is highly malignant because it easily acquires multidrug resistance. We have found that HER2 is upregulated on the cell surface of SCLC cells when they become multidrug-resistant. A HER2 tyrosine kinase inhibitor lapatinib recovered the sensitivity of chemoresistant SCLC cells by inhibiting the function of drug-efflux pumps ABCB1 and ABCG2 which were expressed on them. On the other hand, an anti-HER2 antibody trastuzumab exerted significant antitumor activity toward HER2-upregulated chemoresistant SCLC cells mainly via antibody-dependent cell-mediated cytotoxicity (ADCC) mechanism. Moreover, we treated two patients with HER2-positive relapsed SCLC by trastuzumab plus irinotecan combination therapy and confirmed the antitumor efficacy and safety in this clinical setting. These findings indicate the possibility of HER2 as therapeutic target to overcome multidrug-resistance of SCLC.

Free Research Field

医歯薬学