Identification of biomarkers for novel therapeutic agents in colorectal cancer based on preclinical analysis.

• Project/Area Number: 15K06860
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor diagnostics
• Research Institution: Japanese Foundation for Cancer Research
• Principal Investigator: MITSUKUNI SUENAGA 公益財団法人がん研究会, 有明病院 消化器内科, 医長 (70462223)
• Co-Investigator(Renkei-kenkyūsha): Mashima Tetsuo 公益財団法人がん研究会, がん化学療法センター 分子生物治療研究部, 主任研究員 (30311228) ; Dan Shingo 公益財団法人がん研究会, がん化学療法センター 分子薬理部, 部長 (70332202)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 効果予測マーカー

Outline of Final Research Achievements

Identification of biomarkers for novel agents that highly correspond to clinical outcome is hard to detect in oncology practice. In this study, we performed preclinical omics analysis and translational validation study to identify the candidate biomarkers for regorafenib and TAS-102 efficacy in metastatic colorectal cancer patients. Serum CCL5 and VEGF-A, and CCL5 genotypes were demonstrated as candidate biomarker predicting efficacy and toxicity of regoragfnib. On the other hand, some candidate predictive markers for efficacy of TAS-102 have been recognized by gene expression and database analysis. Further preclinical data-based translational validation study is warranted in metastatic colorectal cancer patients.

Research Products

• [Journal Article] Gene Polymorphisms in the CCL5/CCR5 Pathway as a Genetic Biomarker for Outcome and Hand-Foot Skin Reaction in Metastatic Colorectal Cancer Patients Treated With Regorafenib. (2018)
  • Author(s): Suenaga M, Schirripa M, Cao S, Zhang W, Yang D, Ning Y, Cremolini C, Antoniotti C, Borelli B, Mashima T, Okazaki S, Berger MD, Miyamoto Y, Gopez R Jr., Barzi A, Lonardi S, Yamaguchi T, Falcone A, Loupakis F, Lenz HJ
  • Journal Title: Clin Colorectal Cancer Volume: 印刷中 Issue: 2 Pages: e395-e414
  • DOI: 10.1016/j.clcc.2018.02.010
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Serum VEGF-A and CCL5 levels as candidate biomarkers for efficacy and toxicity of regorafenib in patients with metastatic colorectal cancer. (2016)
  • Author(s): Suenaga M, Mashima T, Kawata N, Wakatsuki T, Horiike Y, Matsusaka S, Dan S, Shinozaki E, Seimiya H, Mizunuma N, Yamaguchi K, Yamaguchi T.
  • Journal Title: Oncotarget. Volume: 7(23) Issue: 23 Pages: 34811-34823
  • DOI: 10.18632/oncotarget.9187
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Identification of biomarkers for TAS-102 efficacy in metastatic colorectal cancer patients based on preclinical analysis and clinical validation. (2018)
  • Author(s): Suenaga, M., Mashima, T., Kawata, N., Dan, S., Wakatsuki, T., Shinozaki, E., Ichimura, T., Ogura, M., Takahari, D., Osumi, H., Ota, Y., Chin, K., Seimiya, H., Yamaguchi, K., Yamaguchi, T.
  • Organizer: ASCO 2018 Gastrointestinal Cancer Symposium
  • Int'l Joint Research
• [Presentation] Matrix metalloproteinase-related gene polymorphisms to predict efficacy of regorafenib in patients with metastatic colorectal cancer. (2018)
  • Author(s): Suenaga, M., Schirripa, M., Cao, S., Zhang, W., Yang, D., Ning, Y., Bergamo, F., Zagonel, V., Rossini, D., Borelli, B., Okazaki, S., Berger, M., Miyamoto, Y., Gopez, R., Barzi, A., Yamaguchi, T., Loupakis, F., Lenz , H.
  • Organizer: ASCO 2018 Gastrointestinal Cancer Symposium
  • Int'l Joint Research
• [Presentation] Role of genetic polymorphisms in CCL5/CCR5 axis to predict efficacy of regorafenib in patients with refractory metastatic colorectal cancer. (2017)
  • Author(s): Suenaga, M., Schirripa, M., Cao, S., Zhang, W., Yang, D., Marmorino, F., Bergamo, F., Antoniotti, C., Rossini, D., Ning, Y., Okazaki, S., Berger , M., Miyamoto, Y., Gopez, R., Hanna, D., Barzi, A., Mashima, T., Yamaguchi, T., Loupakis, F., Lenz , H.
  • Organizer: ASCO 2017 Gastrointestinal Cancer Symposium
  • Int'l Joint Research
• [Presentation] Genetic variants of genes in CCL5/CCR5 pathway to predict regorafenib-induced hand-foot skin reaction in patients with refractory metastatic colorectal cancer: A report of ethnic difference. (2017)
  • Author(s): Suenaga, M., Schirripa, M., Cao, S., Zhang., W., Yang, D., Salvatore, L., Lonardi, S., Moretto, R., Borelli, B., Ning, Y., Okazaki, S., Berger, M., Miyamoto, Y., Gopez, R., Hanna, D., Barzi, A., Wakatsuki, T., Yamaguchi, T., Loupakis, F., Lenz, H.
  • Organizer: ASCO 2017 Gastrointestinal Cancer Symposium
  • Int'l Joint Research
• [Patent(Industrial Property Rights)] マルチキナーゼ阻害剤の有効性と安全性を予測する検査方法、検査キッ ト、及びバイオマー カー (2015)
  • Inventor(s): 末永光邦、水沼信之、馬島哲夫、清宮啓之
  • Industrial Property Rights Holder: 末永光邦、水沼信之、馬島哲夫、清宮啓之
  • Industrial Property Rights Type: 特許
  • Filing Date: 2015-12-24