The impact of bevacizumab on EGFR-TKI and anti-EGFR antibody

• Project/Area Number: 26893155
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Respiratory organ internal medicine
• Research Institution: Okayama University
• Principal Investigator: Ohashi Kadoaki 岡山大学, 大学病院, 助教 (60729193)
• Project Period (FY): 2014-08-29 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 非小細胞肺癌 / EGFRT790M / アファチニブ / セツキシマブ / ベバシツズマブ / EGFR T790M / 肺癌 / EGFR変異

Outline of Final Research Achievements

EGFR mutations is major oncogenic driver mutation in non-smoking related lung cancers. EGFR-TKI is standard therapy for the lung cancers, however acquired resistance is inevitable. Secondary acquired mutation, EGFR T790M is major cause of the resistance.This pre-clinical reserach focused on the effect of triplet therapy with EGFR-TKI(afatinib), anti-EGFR antibody(cetuximab) and anti VEGF antibody(bevacizumab). Lung adenocarcinoma cell lines harboring EGFR T790M, H1975 and RPC-9 cell lines were transplanted in nude mice for xenograft models. The effect of each monotherapies or double therapies were moderate in the mice models. In contrast, the triplet therapy recurrently induced complete remission in the mice models.

Research Products

• [Journal Article] NF-κB drives acquired resistance to a novel mutant-selective EGFR inhibitor. (2015)
  • Author(s): Galvani E, Sun J, Leon LG, Sciarrillo R, Narayan RS, Sjin RT, Lee K, Ohashi K, Heideman DA, Alfieri RR, Heynen GJ, Bernards R, Smit EF, Pao W, Peters GJ, Giovannetti E.
  • Journal Title: Oncotarget Volume: ６ Issue: 40 Pages: 42717-32
  • DOI: 10.18632/oncotarget.3956
  • Peer Reviewed / Int'l Joint Research
• [Presentation] The impact of bevacizumab on combination low-dose afatinib and cetuximab therapy in lung cancer cells harboring activated EGFR mutations (2015)
  • Author(s): Kenichiro Kudo, Kadoaki Ohashi, Eiki Ichihara, Daisuke Minami, Hisao Kubo, Akiko Sato, Yuka Kato, Hideko Isozaki, Hiroe Kayatani, Tomoki Tamura, Mitsune Tanimoto, and Katsuyuki Kiura
  • Organizer: American Asociation of Cancer Research Annual meeting 2015
  • Place of Presentation: Pennsylvania Convention Center Philadelphia, Pennsylvania, USA
  • Year and Date: 2015-04-19
  • Int'l Joint Research
• [Presentation] The impact of bevacizumab on combination low-dose afatinib and cetuximab therapy in lung cancer cells harboring activated EGFR mutations (2015)
  • Author(s): Kenichiro Kudo, Kadoaki Ohashi, Eiki Ichihara,Toshio Kubo, Daisuke Minami, Akiko Sato,Katsuyuki Hotta, Mitsune Tanimoto, Katsuyuki Kiura
  • Organizer: AACR Annual Meeting 2015
  • Place of Presentation: Pennsylvania Convention Center Philadelphia, Pennsylvania
  • Year and Date: 2015-04-19
• [Presentation] The impact of bevacizumab on combination low-dose afatinib and cetuximab therapy in lung cancer cells harboring activated EGFR mutations (2015)
  • Author(s): Kenichiro Kudo, Kadoaki Ohashi, Eiki Ichihara, Daisuke Minami, Hisao Kubo, Akiko Sato, Yuka Kato, Hideko Isozaki, Hiroe Kayatani, Tomoki Tamura, Mitsune Tanimoto, and Katsuyuki Kiura
  • Organizer: 第５５回日本呼吸器学会学術講演会
  • Place of Presentation: 東京国際フォーラム、東京
  • Year and Date: 2015-04-18
• [Presentation] The impact of bevacizumab on combination low-dose afatinib and cetuximab therapy in lung cancer cells harboring activated EGFR mutations (2015)
  • Author(s): Kenichiro Kudo, Kadoaki Ohashi, Eiki Ichihara,Toshio Kubo, Daisuke Minami, Akiko Sato,Katsuyuki Hotta, Mitsune Tanimoto, Katsuyuki Kiura
  • Organizer: 第55回日本呼吸器学会学術講演会
  • Place of Presentation: 東京
  • Year and Date: 2015-04-18