A novel noninvasive screening assay for RAS mutations in the peripheral blood sample using next-generation sequencing for anti-EGFR antibodies therapy

• Project/Area Number: 26462013
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Sapporo Medical University (2015-2017); Osaka University (2014)
• Principal Investigator: Takemasa Ichiro 札幌医科大学, 医学部, 教授 (50379252)
• Co-Investigator(Kenkyū-buntansha): 水島 恒和 大阪大学, 医学系研究科, 寄附講座教授 (00527707) ; 山本 浩文 大阪大学, 医学系研究科, 教授 (30322184) ; 佐藤 太郎 大阪大学, 医学系研究科, 寄附講座教授 (40368303) ; 畑 泰司 大阪大学, 医学系研究科, 助教 (70644912)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 大腸癌 / 非侵襲性KRAS変異検査 / 次世代シーケンサー / 感受性性診断 / 感受性診断 / 大腸がん

Outline of Final Research Achievements

Because the effect of anti-EGFR antibodies in advanced colorectal cancer is limited to RAS wild type patients, it is necessary to select the patients by the genetic screening assay of the cancer tissue including the biopsy sample before the treatment. In addition, RAS mutations will be acquired during anti-EGFR antibodies therapy. Detection of a low-frequency clone with RAS mutations in the plasma during anti-EGFR antibodies therapy make it possible to identify the patient for an useful treatment and to evade continuation of an useless treatment. This approach is expected to improve the clinical outcomes and a nationwide cost-effectiveness of this treatment. A novel noninvasive screening assay for RAS mutations in the blood sample using next-generation sequencing as liquid biopsy was established in this study and our methods will help molecular monitoring of the disease over the time is necessary to identify mechanisms of resistance and to adapt the therapy to the new molecular target.

Research Products

• [Journal Article] ST6GALNAC1 plays important roles in enhancing cancer stem phenotypes of colorectal cancer via the Akt pathway (2017)
  • Author(s): Ogawa T, Hirohashi Y, Murai A, Nishidate T, Okita K, Wang L, Ikehara Y, Satoyoshi T, Usui A, Kubo T, Nakastugawa M, Kanaseki T, Tsukahara T, Kutomi G, Furuhata T, Hirata K, Sato N, Mizuguchi T, Takemasa I, Torigoe T.
  • Journal Title: Oncotartget Volume: 8 Pages: 112550-112564
  • DOI: 10.18632/oncotarget.22545
  • Peer Reviewed / Open Access
• [Journal Article] Downregulation of serum metabolite GTA-446 as a novel potential marker for early detection of colorectal cancer (2017)
  • Author(s): Hata T, Takemasa I, Takahashi H, Haraguchi N, Nishimura J, Hata T, Mizushima T, Doki Y, Mori M
  • Journal Title: J Cancer Volume: 117 Pages: 227-232
  • DOI: 10.1038/bjc.2017.163
  • Peer Reviewed / Open Access