The new strategy for lung cancer treatment by Hsp90 inhibitors and radiation therapy

• Project/Area Number: 24791462
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Thoracic surgery
• Research Institution: Okayama University
• Principal Investigator: YAMAMOTO Hiromasa 岡山大学, 大学病院, 助教 (40467733)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 原発性肺癌 / Hsp90阻害剤 / 放射線治療 / EGFRチロシンキナーゼ阻害剤耐性

Outline of Final Research Achievements

We evaluated the radiosensitizing effect of Hsp90 inhibitor, NVP-AUY922 (AUY), on NSCLC cell lines harboring EGFR activating mutations and showing acquired resistance to EGFR-TKIs via any of several mechanisms. AUY was more effective against the gefitinib-resistant sublines with T790M mutation and MET amplification than against the parental cell lines, although the subline with stem cell-like properties showed more than a 10-fold higher resistance to AUY than the parental cell line. AUY exerted a significant radiosensitizing effect on the parental cell line and the MET-amplified subline through inducing G2/M arrest and inhibition of non-homologous end joining (NHEJ). In contrast, the radiosensitizing effect of AUY was limited on the subline with stem cell-like properties, in which it did not induce G2/M arrest or inhibition of NHEJ.

Research Products

• [Journal Article] Hsp90 inhibitor NVP-AUY922 enhances the radiation sensitivity of lung cancer cell lines with acquired resistance to EGFR-tyrosine kinase inhibitors. (2015)
  • Author(s): Hashida S, Yamamoto H, Shien K, Ohtsuka T, Suzawa K, Maki Y, Furukawa M, Soh J, Asano H, Tsukuda K, Miyoshi S, Kanazawa S, Toyooka S
  • Journal Title: Oncology Reports Volume: 33 Issue: 3 Pages: 1499-1504
  • DOI: 10.3892/or.2015.3735
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Effect of Hsp90 inhibitor NVP-AUY922 with radiation on lung adenocarcinoma cell lines with acquired resistance to EGFR-tyrosine kinase inhibitors (2015)
  • Author(s): Yuho Maki, Shinsuke Hashida, Hiromasa Yamamoto, Kazuhiko Shien, Tomoaki Ohtsuka, Ken Suzawa, Masashi Furukawa, Junichi Soh, Hiroaki Asano, Kazunori Tsukuda, Shinichiro Miyoshi, Susumu Kanazawa, Shinichi Toyooka.
  • Organizer: AACR Annual Meeting 2015
  • Place of Presentation: Philadelphia, PA, USA
  • Year and Date: 2015-04-18 – 2015-04-22