Estimation of effects of EGFR-TKI on NSCLCs by cell-based approach including CTOS

• Project/Area Number: 24790829
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Respiratory organ internal medicine
• Research Institution: 地方独立行政法人宮城県立病院機構宮城県立がんセンター(研究所)
• Principal Investigator: WATANUKI ZENTA 地方独立行政法人宮城県立病院機構宮城県立がんセンター(研究所), がん先進治療開発研究部, 特任研究員 (10626518)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 癌 / 肺癌 / EGFR-TKI / CTOS

Research Abstract

EGFR-TKIs work effectively on NSCLCs with EGFR-mutations, however, most of the cases eventually develop drug resistance by acquiring an additional mutation T790M. In the present study, I aimed to establish a CTOS system; a spheroid culture system with patient derived cancer cells. Initial CTOS trial worked fine. Nevertheless, due to the relatively slow rate of tumors, I established another cell-based EGFR-TKI evaluation system. Forced expression of EGFR, either wild type or mutations, enabled K562 cells to grow and survive by the help of the EGFR-driven signals. EGFR-TKI killed the cells, in a dose-dependent manner. Among the genotypes tested, L858R was the most sensitive, whereas L858R/L790M showed resistance to the first generation TKIs. I found that EGFR-TKI-induced cell death was correlated with BIMEL induction and autophagy.

Research Products

• [Presentation] Combining Afatinib and Cetuximab synergistically increases their cytotoxicity for EGFR T790M-harboring cells (2014)
  • Author(s): Nobuyuki Tanaka, Zenta Watanuki, Tatsuro Fukuhara, Makoto Maemondo
  • Organizer: AACR2014
  • Place of Presentation: San Diego, USA
• [Presentation] A Case of Small Cell Lung Cancer with Cancer-Associated Retinopathy (CAR) Accompanied by Circulating Anti-CRMP5/CV2 Antibodies (2013)
  • Author(s): Mami Morita, Tatsuro Fukuhara, Yoko Tsukita, Zenta Watanuki, Aya Suzuki, Kana Watanabe, Nobuyuki Sato, Hidetoshi Takahashi, Shigemi Ito, Ikuro Sato, and Makoto Maemondo
  • Organizer: 18th Congress of the Asian Pacific Society of Respirology
  • Place of Presentation: Yokohama