Interpretation for the mechanism of acquired resistance of EGFR blockade by using cell free DNA

• Project/Area Number: 26462030
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Nippon Medical School
• Principal Investigator: Yamada Takeshi 日本医科大学, 医学部, 准教授 (50307948)
• Co-Investigator(Kenkyū-buntansha): 小泉 岐博 日本医科大学, 医学部, 助教 (40328802)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
• Keywords: 大腸癌 / 抗EGFR抗体 / Liquid biopsy / Circulating DNA / Circulating tumor DNA / liquid biopsy / 循環DNA / circulating tumor DNA / circulating DNA / KRAS / 薬剤耐性 / cell free DNA / 2次耐性

Outline of Final Research Achievements

KRAS mutation is detected in circulating cell-free DNA of 10% of patients with KRAS wild colorectal cancer. EGFR blockade has no cyto-reductive effect in those patients. EGFR blockade has cyto-reductive effect in patients with both KRAS and BRAF wild in primary tumor and circulating cell free DNA. KRAS mutation is detected in circulating cell free DNA of 80% of patients who have got acquired resistance to EGFR blockade. Also, BRAF mutation is detected in circulating cell free DNA of 40% of patients who have got acquired resistance to EGFR blockade.

Research Products

• [Journal Article] Utility of KRAS mutation detection using circulating cell-free DNA from patients with colorectal cancer (2016)
  • Author(s): Takeshi Yamada, Goro Takahashi, Takuma Iwai, et al.
  • Journal Title: Cancer Science Volume: 107 Issue: 7 Pages: 936-43
  • DOI: 10.1111/cas.12959
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Utility of KRAS mutation detection using circulating cell-free DNA from patients with colorectal cancer (2016)
  • Author(s): 山田岳史
  • Journal Title: Cancer Science Volume: 未定
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Emergence of KRAS mutations contributes to acquired resistance to EGFR blockade (2017)
  • Author(s): Takeshi Yamada
  • Organizer: American Association for Cancer Research
  • Place of Presentation: Washington
  • Year and Date: 2017-04-01
• [Presentation] Tracking emerging KRAS, BRAF and EGFR mutations through circulating cell-free DNA in patients with colorectal cancers treated by epidermal growth factor receptor blockade (2017)
  • Author(s): Takeshi Yamada
  • Organizer: ASCO-Gastrointestinal Cancer Symposium
  • Place of Presentation: San Francisco
  • Year and Date: 2017-02-19
• [Presentation] Tracking emerging KRAS and BRAF mutations through ccfDNA in colorectal cancers treated with EGFR blockade (2016)
  • Author(s): Takeshi Yamada
  • Organizer: European Society for Medical Oncology
  • Place of Presentation: Copenhagen
  • Year and Date: 2016-10-07
  • Int'l Joint Research
• [Presentation] Prediction and response evaluation of EGFR blockade for colorectal cancer by using circulating cell free DNA (2016)
  • Author(s): Takeshi Yamada
  • Organizer: American Association for Cancer Research
  • Place of Presentation: New Orleans
  • Year and Date: 2016-04-16
  • Int'l Joint Research
• [Presentation] Prediction and response evaluation of EGFR blockade for colorectal cancer by using circulating cell free DNA (2015)
  • Author(s): 岩井拓磨、山田岳史
  • Organizer: AACR2015
  • Place of Presentation: Philadelphia
  • Year and Date: 2015-04-18
  • Int'l Joint Research
• [Presentation] Real time personalized therapy for colorectal cancer by using liquid biopsy (2014)
  • Author(s): Yamada T, Kan H, Matsumoto S, Koizumi M, Shinji S, Matsuda A, Yamagishi A, Yokoyama Y, Iwai T, Uchida E
  • Organizer: 第25回日本消化器癌発生学会総会
  • Place of Presentation: 福岡
  • Year and Date: 2014-11-13 – 2014-11-14
• [Presentation] Prediction for efficacy and resistance of EGFR blockade by using liquid biopsy (2014)
  • Author(s): Yamada T, Kan H, Uchida E
  • Organizer: Japan Digestive Disease Week 2014
  • Place of Presentation: 神戸
  • Year and Date: 2014-10-23
• [Presentation] Liquid biopsy detection of KRAS and BRAF mutations may be useful as a prognostic or predictive marker (2014)
  • Author(s): T.Yamada
  • Organizer: European society for medical oncology 40
  • Place of Presentation: Madrid
  • Year and Date: 2014-09-26 – 2014-09-30
• [Presentation] An Ultrasensitive Molecular Diagnostic Method for Blood Biopsy in Personalized Treatment of Colorectal Cancer (2014)
  • Author(s): S. Kitano, T. Yamada
  • Organizer: European society for medical oncology 40
  • Place of Presentation: Madrid
  • Year and Date: 2014-09-26 – 2014-09-30
• [Presentation] 大腸癌分子治療におけるliquid biopsyを利用したreal-time personalized therapy (2014)
  • Author(s): 山田岳史
  • Organizer: 第69回日本消化器外科学会
  • Place of Presentation: 郡山
  • Year and Date: 2014-07-16 – 2014-07-18