Development of predictive marker of drug therapy for colorectal cancer by epigenetic analysis of circulating DNA

2011 Fiscal Year Final Research Report

• Project/Area Number: 21590802
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Tohoku University
• Principal Investigator: SHIMODAIRA Hideki 東北大学, 病院, 講師 (70373214)
• Co-Investigator(Kenkyū-buntansha): TAKAHASHI Masanobu 東北大学, 病院, 助教 (00447161)
• Project Period (FY): 2009 – 2011
• Keywords: 下部消化管学

Research Abstract

Forty three chemotherapy-refractory Japanese patients with mCRC were treated with cetuximab monotherapy or cetuximab plus irinotecan. KRAS, BRAF and PIK3CA mutational status of tumors were assessed. The wild-type subgroup without any mutations in the KRAS, BRAF and PIK3CA had a better RR (37. 0%)and PFS (6. 4 months)than did the wild-type KRAS subgroup. Our data indicated that KRAS status is predictive of cetuximab response in the Japanese population. The additional analysis of BRAF and PIK3CA genes in wild-type KRAS patients could improve the selection of the patients who are most likely to benefit from anti-EGFR antibody therapy.

Research Products

• [Journal Article] Clinical usefulness of KRAS, BRAF and PIK3CA mutations as predictive markers of cetuximab efficacy in irinotecan-and oxaliplatin-refractory Japanese patients with metastatic colorectal cancer (2012)
  • Author(s): Soeda, H., Shimodaira, H., Watanabe, M., Suzuki, T., Gamoh, M., Mori, T., Komine, K., Iwama, N., Kato, S., Ishioka, C.
  • Journal Title: Int J Clin Oncol Volume: (in press)
  • Peer Reviewed
• [Journal Article] 分子標的治療薬におけるバイオマーカーの役割大腸癌における抗EGFR抗体薬のバイオマーカー (2011)
  • Author(s): 添田大司, 下平秀樹, 石岡千加史
  • Journal Title: 癌と化学療法 Volume: 38巻7号 Pages: 1079-1083
• [Journal Article] 進行再発大腸癌における抗EGFR抗体薬の適応宿主ADCC活性と抗EGFR抗体 (2010)
  • Author(s): 下平秀樹, 小峰啓吾, 添田大司, 石岡千加史
  • Journal Title: 癌と化学療法 Volume: 37 Pages: 795-798
• [Journal Article] 分子標的薬とシグナル伝達大腸癌における抗EGFR抗体薬と分子マーカーとしてのEGFRを介したシグナル伝達因子 (2009)
  • Author(s): 下平秀樹, 添田大司, 小峰啓吾, 石岡千加史
  • Journal Title: 癌と化学療法 Volume: 36巻7号 Pages: 1063-1066
• [Presentation] 石岡千加史:大腸癌におけるEGFRシグナル伝達経路の変異とオキサリプラチン、イリノテカンの治療成績 (2011)
  • Author(s): 添田大司, 下平秀樹, 渡辺みか, 森隆弘, 角道祐一, 高橋信, 秋山聖子, 小峰啓吾, 加藤俊介
  • Organizer: 第108回日本内科学会学術講演会
  • Place of Presentation: 東京で予定されていた学術講演会は、震災のため開催されず
  • Year and Date: 2011-02-20
• [Presentation] 石岡千加史:大腸癌における抗EGFR抗体薬のバイオマーカーEGFRシグナル伝達因子検索の意義 (2010)
  • Author(s): 添田大司, 下平秀樹, 小峰啓吾, 加藤俊介, 森隆弘, 角道祐一, 大堀久詔, 高橋信, 秋山聖子, 鈴木貴夫, 蒲生真紀夫, 渡辺みか, 岩間憲行, 鈴木博義
  • Organizer: 第48回日本癌治療学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2010-10-29
• [Presentation] Genetic alterations in colorectal cancer associated with the efficacy of anti-EGFR antibody or cancer predisposition (2009)
  • Author(s): Shimodaira, H., Soeda, H., Takahashi, M., Ishioka, C.
  • Organizer: The 14th Korea-Japan Cancer Research Workshop
  • Place of Presentation: 金沢
  • Year and Date: 2009-12-19
• [Presentation] Status of EGFR related signal transduction for predicting response to anti-EGFR therapy in advanced colorectal cancer (2009)
  • Author(s): Shimodaira, H., Soeda, H., Takahashi, M., Ishioka, C.
  • Organizer: The 68th Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-01
• [Book] 分子標的治療薬その他の開発中の小分子物質Apoptosis促進剤、mTOR阻害剤、サリドマイド、レナリドマイド、その他 (2009)
  • Author(s): 下平秀樹
  • Total Pages: 184-188
  • Publisher: 中外医学社
• [Remarks] 日刊薬業2009年10月5日に第68回日本癌学会総会での発表について報道
  • URL: http://www.co.idac.tohoku.ac.jp/staff/shimohira.html