Significance of CIMP as a biomarker for chemotherapy in colorectal cancer

• Project/Area Number: 26460958
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Tohoku University
• Principal Investigator: Shimodaira Hideki 東北大学, 加齢医学研究所, 准教授 (70373214)
• Research Collaborator: ZHANG XIAFEI 東北大学, 大学院生 ; SOEDA HIROSHI 東北大学, 大学院生
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: CpG アイランド / メチル化 / がん薬物療法 / バイオマーカー / CpGアイランドメチル化 / 抗VEGF抗体 / 大腸癌

Outline of Final Research Achievements

The CpG island methylator phenotype (CIMP) with multiple promoter methylated loci has been observed in a subset of human colorectal cancer (CRC) cases. CIMP status, which is closely associated with specific clinicopathological and molecular characteristics, is considered a potential predictive biomarker for efficacy of cancer treatment. The progression-free survival of patients with CIMP-positive tumors receiving sequential therapy with FOLFOX as the first-line treatment followed by irinotecan-based therapy as the second-line treatment was inferior to that of such patients receiving the reverse sequence. Furthermore, CIMP-positive tumors showed higher mutation frequencies for the five EGFR-related genes than the CIMP-negative tumors did. Among the KRAS wild-type tumors, CIMP-positive tumors were associated with a worse clinical outcome than CIMP-negative tumors following anti-EGFR antibody therapy.

Research Products

• [Journal Article] CpG island methylator phenotype is associated with the efficacy of sequential oxaliplatin- and irinotecan-based chemotherapy and EGFR-related gene mutation in Japanese patients with metastatic colorectal cancer. (2016)
  • Author(s): Zhang, X.，Shimodaira, H.，Soeda, H.，Komine, K.，Takahashi, H.，Ouchi, K.，Inoue, M.，Takahashi, M.，Takahashi, S.，Ishioka, C.
  • Journal Title: Int J Clin Oncol Volume: 21 Issue: 6 Pages: 1091-1101
  • DOI: 10.1007/s10147-016-1017-6
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] OLA1 gene sequencing in patients with BRCA1/2 mutation-negative suspected hereditary breast and ovarian cancer. (2016)
  • Author(s): Takahashi M*, Chiba N*, Shimodaira H, Yoshino Y, Mori T, Sumii M, Nomizu T, Ishioka C.
  • Journal Title: Breast Cancer Volume: 24(2) Issue: 2 Pages: 336-340
  • DOI: 10.1007/s12282-016-0709-0
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Successful sequential treatment of a patient with advanced gastrointestinal stromal tumor using four different molecularly targeted drugs. (2016)
  • Author(s): Sugiyama S, Ishizuka M, Takahashi M, Komine K, Imai H, Saijo K, Takahashi M, Shirota H, Takahashi S, Shimodaira H, Ishioka C.
  • Journal Title: International Cancer Conference Journal Volume: 5 Issue: 4 Pages: 163-7
  • DOI: 10.1007/s13691-016-0250-1
• [Journal Article] Efficacy and Safety Assessment of Paclitaxel in Patients with Docetaxel-Resistant Esophageal Squamous Cell Carcinoma. (2016)
  • Author(s): Imai H, Komine K, Takahashi S, Saijo K, Okada Y, Kobayashi A, Okita A, Chikamatsu S, Kasahara Y, Takahashi M, Oishi T, Shirota H, Takahashi M, Shimodaira H, Ishioka C.
  • Journal Title: Chemotherapy Volume: 61 Issue: 5 Pages: 262-8
  • DOI: 10.1159/000444122
  • Peer Reviewed
• [Journal Article] Attainment of a Long-term Favorable Outcome by Sunitinib Treatment for Pancreatic Neuroendocrine Tumor and Renal Cell Carcinoma Associated with von Hippel-Lindau Disease (2016)
  • Author(s): Kobayashi A, Takahashi M, Imai H, Akiyama S, Sugiyama S, Komine K, Saijo K, Takahashi M, Takahashi S, Shirota H, Sato N, Fujishima F, Shuin T, Shimodaira H, Ishioka C.
  • Journal Title: Internal Medicine Volume: 55 Issue: 6 Pages: 629-634
  • DOI: 10.2169/internalmedicine.55.5796
  • NAID: 130005138072
  • ISSN: 0918-2918, 1349-7235
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Efficacy and Safety of Carboplatin and Etoposide Combination Chemotherapy for Extrapulmonary Neuroendocrine Carcinoma: A Retrospective Case Series. (2016)
  • Author(s): Imai H, Shirota H, Okita A, Komine K, Saijo K, Takahashi M, Takahashi S, Takahashi M, Shimodaira H, Ishioka C.
  • Journal Title: Chemotherapy Volume: 61（３） Issue: 3 Pages: 111-116
  • DOI: 10.1159/000441551
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] DNA methylation status as a biomarker of anti-epidermal growth factor receptor treatment for metastatic colorectal cancer. (2015)
  • Author(s): Ouchi K, Takahashi S, Yamada Y, Tsuji S, Tatsuno K, Takahashi H, Takahashi N, Takahashi M, Shimodaira H, Aburatani H, Ishioka C.
  • Journal Title: Cancer Science Volume: 106 Issue: 12 Pages: 1722-1729
  • DOI: 10.1111/cas.12827
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Gene-expression profiles correlate with the efficacy of anti-EGFR therapy and chemotherapy for colorectal cancer. (2015)
  • Author(s): Inoue M, Takahashi S, Soeda H, Shimodaira H, Watanabe M, Miura K, Sasaki I, Kato S, Ishioka C.
  • Journal Title: Int J Clin Oncol. Volume: 20 Issue: 6 Pages: 1147-55
  • DOI: 10.1007/s10147-015-0841-4
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Functional Complementation Assay for 47 MUTYH Variants in a MutY-Disrupted Escherichia coli Strain. (2015)
  • Author(s): Komine K, Shimodaira H, Takao M, Soeda H, Zhang X, Takahashi M, Ishioka C.
  • Journal Title: Human Mutation Volume: 36 Issue: 7 Pages: 704-711
  • DOI: 10.1002/humu.22794
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Phase II trial of cetuximab plus irinotecan for oxaliplatin- and irinotecan-based chemotherapy-refractory patients with advanced and/or metastatic colorectal cancer: evaluation of efficacy and safety based on KRAS mutation status (T-CORE0801). (2014)
  • Author(s): Soeda H., Shimodaira H., Gamoh M., Ando H., Isobe H., Suto T., Takahashi S., Kakudo Y., Amagai K., Mori T., Watanabe M., Yamaguchi T.vKato S., Ishioka C.
  • Journal Title: Oncology Volume: 87 Issue: 1 Pages: 7-20
  • DOI: 10.1159/000360989
  • Peer Reviewed / Open Access
• [Presentation] 2.FOLFIRINOX療法およびGEM+nabPTX療法導入後の進行膵癌患者の生存期間の後ろ向き解析 (2016)
  • Author(s): 近松園子，高橋昌宏，山田英晴，沖田啓，小林輝大，佐藤悠子，大内康太，岡田佳也，小峰啓吾，西條憲，今井源，高橋信，高橋雅信，下平秀樹，石岡千加史
  • Organizer: 第54回日本癌治療学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2016-10-20
• [Presentation] 切除不能進行再発大腸癌におけるtrifluridine/tipiracil hydrochlorideとregorafenib投与例の後方視的検討 (2016)
  • Author(s): 笠原佑紀、近松園子、西條憲、小峰啓吾、今井源、高橋昌宏、城田英和、高橋信、高橋雅信、下平秀樹、石岡千加史
  • Organizer: 第14回日本臨床腫瘍学会学術集会
  • Place of Presentation: 神戸
  • Year and Date: 2016-07-28
• [Presentation] 進行骨軟部肉腫に対するゲムシタビン・ドセタキセル併用療法の効果・安全性に関する後方視的解析 (2016)
  • Author(s): 高橋雅信、岡田佳也、小峰啓吾、今井源、西條憲、高橋昌宏、高橋信、千葉奈津子、森隆弘、下平秀樹、石岡千加史
  • Organizer: 第14回日本臨床腫瘍学会学術集会
  • Place of Presentation: 神戸
  • Year and Date: 2016-07-28
• [Presentation] A retrospective analysis for efficacy and safety of Gemcitabine plus nab-Paclitaxel in advanced pancreatic cancer (2016)
  • Author(s): 岡田佳也、小林輝大、大石隆之、西條憲、高橋昌宏、高橋雅信、城田英和、下平秀樹、森隆弘、石岡千加史
  • Organizer: 第14回日本臨床腫瘍学会学術集会
  • Place of Presentation: 神戸
  • Year and Date: 2016-07-28
• [Presentation] Geriatric assessment using G8 screening tool in elderly patients with unresectable or metastatic gastrointestinal cancer (2016)
  • Author(s): 高橋昌宏、小林輝大、沖田啓、伊藤祝栄、佐藤悠子、高橋信、高橋雅信、城田英和、下平秀樹、石岡千加史
  • Organizer: 第14回日本臨床腫瘍学会学術集会
  • Place of Presentation: 神戸
  • Year and Date: 2016-07-28
• [Presentation] 脂肪肉腫の治療薬の臨床開発 オーバービュー (2015)
  • Author(s): 下平秀樹
  • Organizer: 日本肉腫学会記念シンポジウム
  • Place of Presentation: 京都平安ホテル（京都府、京都市）
  • Year and Date: 2015-12-03
  • Invited
• [Presentation] The G8 geriatric screening tool for elderly patients with unresectable or metastatic gastrointestinal cancer (2015)
  • Author(s): 高橋昌宏、・・、下平秀樹 他
  • Organizer: 第13回日本臨床腫瘍学会学術集会
  • Place of Presentation: ロイトン札幌（北海道、札幌市）
  • Year and Date: 2015-07-16
• [Presentation] 治癒切除不能進行膵癌におけるFOLFIRINOX療法の有効性および安全性に関する後方視的検討 (2015)
  • Author(s): 小林輝大、・・、下平秀樹 他
  • Organizer: 第13回日本臨床腫瘍学会学術集会
  • Place of Presentation: ロイトン札幌（北海道、札幌市）
  • Year and Date: 2015-07-16
• [Presentation] 小腸癌における5FU系薬剤による治癒成績の後方視的解析 (2015)
  • Author(s): 今井源、・・、下平秀樹 他
  • Organizer: 第13回日本臨床腫瘍学会学術集会
  • Place of Presentation: ロイトン札幌（北海道、札幌市）
  • Year and Date: 2015-07-16
• [Presentation] 軟部肉腫に対するドキソルビシン＋イフォスファミド併用療法の治療成績についての後方視的検討 (2015)
  • Author(s): 西條憲、・・、下平秀樹 他
  • Organizer: 第13回日本臨床腫瘍学会学術集会
  • Place of Presentation: ロイトン札幌（北海道、札幌市）
  • Year and Date: 2015-07-16
• [Presentation] CpG island methylator phenotype is associated with the efficacy of chemotherapy for metastatic colorectal cancer (2014)
  • Author(s): 張暁飛、下平秀樹、添田大司、小峰啓吾、井上正広、高橋秀和、高橋雅信、高橋信、加藤俊介、石岡千加史
  • Organizer: EUROPEAN SOCIETY FOR MEDICAL ONCOLOGY
  • Place of Presentation: Madrid
  • Year and Date: 2014-09-26 – 2014-09-30
• [Presentation] CpGアイランドメチル化表現型とイリノテカン、オキサリプラチンベースの化学療法の治療成績およびEGFR関連遺伝子変異との相関 (2014)
  • Author(s): 張暁飛、下平秀樹、添田大司、小峰啓吾、井上正広、高橋秀和、高橋雅信、高橋信、加藤俊介、石岡千加史
  • Organizer: 第12回日本臨床腫瘍学会
  • Place of Presentation: 福岡
  • Year and Date: 2014-07-17 – 2014-07-19
• [Book] がん薬物療法時の腎障害診療ガイドライン (2016)
  • Author(s): 下平秀樹
  • Total Pages: 46
  • Publisher: ライフサイエンス出版
• [Book] 次世代のがん治療薬・診断のための研究開発 (2016)
  • Author(s): 下平秀樹
  • Total Pages: 400
  • Publisher: 技術情報協会
• [Book] 家族性腫瘍 (2015)
  • Author(s): 石岡千加史、富田尚裕、野水整、吉田輝彦、宇都宮譲二、福島義光、山内泰子、水谷修紀、谷内江昭宏、東元健、福岡みずき、玉井裕也、田中潔、向井徳男、久保宜明、池田史圭、鈴木眞一、柴田浩行、小峰啓吾、高橋雅信、下平秀樹 他
  • Total Pages: 607
  • Publisher: 日本臨床
• [Book] 新臨床腫瘍学 (2015)
  • Author(s): 日本臨床腫瘍学会編集、石岡千加史、河野隆志、稲沢譲治、大場雄介、曽和義弘、大塚和令、福井忠久、笹原由理子、高橋雅信、高橋信、加藤俊介、高野利実、佐治重衡、上野誠、松本光史、伊藤薫樹、石澤賢一、高橋昌宏、下平秀樹 他
  • Total Pages: 738
  • Publisher: 南江堂