| Project/Area Number |
26860606
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Osaka University |
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Principal Investigator |
MINAMI TOSHIYUKI 大阪大学, 医学(系)研究科(研究院), 助教 (00705113)
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| Co-Investigator(Kenkyū-buntansha) |
MORIMURA OSAMU 大阪大学, 大学院医学系研究科, 院生 (80743765)
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 小細胞肺癌 / 抗癌剤耐性 / 分子標的治療 / HER2 / EphA2 / trastuzumab / T-DM1 / dasatinib / Dasatinib / ADCC |
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| Outline of Final Research Achievements |
Therapeutic strategy against small-cell lung cancer (SCLC) has not improved over the last two decades. We examined the potential of HER2 and EphA2 as therapeutic targets in SCLC. We first evaluated HER2 expression by immunohistochemistry. HER2 expression was detected in 28% of diagnostic biopsy SCLC specimens. Then, we performed trastuzumab plus irinotecan combination therapy in two patients with HER2-positive SCLC. This combination therapy resulted in successful disease control in both patients. We next validated the antitumor activity of trastuzumab emtansine (T-DM1) in SCLC. T-DM1 induced apoptosis and suppressed the growth of HER2-positive irinotecan resistant SCLC xenografts in mice. We further evaluated the biological effects of EphA2 inhibition. EphA2 knockdown and functional inhibition by dasatinib brought about senescence in EphA2-positive SCLC cells, and inhibited their proliferation.
These results indicate that HER2 and EphA2 could be novel therapeutic candidates in SCLC.
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