Search for pathological diagnosis using circulation tumor cells in gastrointestinal cancer

• Project/Area Number: 16K19381
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: National Cancer Center Japan
• Principal Investigator: Shoji Hirokazu 国立研究開発法人国立がん研究センター, 中央病院, 医員 (50765568)
• Research Collaborator: Honda Kazufumi
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2017: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: circulating tumor cell / circulating tumor DNA / gastrointestinal cancer / liquid biopsy / 末梢循環腫瘍細胞 / 消化管がん / リキッドバイオプシー / 次世代シークエンス / 1細胞オミクス解析 / バイオマーカー / オミクス解析

Outline of Final Research Achievements

We established a method employing a label-free inertial microfluidics approach (LFIMA) with next-generation sequencing (NGS) for the analysis of genomic alterations in circulating tumor cells (CTCs) isolated from patients with gastrointestinal (GI) cancer. CTCs could be isolated from a total of 20 peripheral blood cases, including advanced gastrointestinal cancer.In addition, we carried out blood-based molecular profiling to identify actionable drug targets, monitor drug resistance, and track tumor dynamics using CTCs and ctDNA from patients with metastatic colorectal cancer (CRC).

Academic Significance and Societal Importance of the Research Achievements

CTCs から消化管がんの「がんの個性診断法」を実現できれば、最少侵襲で時々刻々変化するがん細胞に対して「適時・最適医療」を提示できるようになると考え、本研究を進めてきた。そして分離したCTCsからの遺伝子変異解析、メタボローム解析が可能でることを証明した。今後は本技術を用いて臨床試験への応用、そしてCTCsの細胞培養が実現できれば、プロテオーム解析や薬剤感受性試験につながり、個々の患者に適した薬剤の提供につながる可能性があり、国内外へのインパクトが非常に高いと考える。また、LFIMAによる診断技術の創出は他の医工学分野の発展にもつながり、新しい医工学の学術領域を創出できる可能性がある。

Research Products

• [Journal Article] Induction chemotherapy with docetaxel, cisplatin and fluorouracil followed by concurrent chemoradiotherapy for unresectable sinonasal undifferentiated carcinoma: Two cases of report. (2019)
  • Author(s): Watanabe S, Honma Y, Murakami N, Igaki H, Mori T, Hirano H, Okita N, Shoji H, Iwasa S, Takashima A, Kato K, Kobayashi K, Matsumoto F, Yoshimoto S, Itami J, Boku N.
  • Journal Title: World J Clin Cases. Volume: 7(6) Issue: 6 Pages: 765-772
  • DOI: 10.12998/wjcc.v7.i6.765
  • Peer Reviewed / Open Access
• [Journal Article] Serum level of octanoic acid predicts the efficacy of chemotherapy for colorectal cancer. (2019)
  • Author(s): Iemoto T, Nishiumi S, Kobayashi T, Fujigaki S, Hamaguchi T, Kato K, Shoji H, Matsumura Y, Honda K, Yoshida M.
  • Journal Title: Oncol Lett. Volume: 17(1) Pages: 831-842
  • DOI: 10.3892/ol.2018.9731
  • NAID: 120006554635
  • Peer Reviewed / Open Access
• [Journal Article] Association between UGT1A1 gene polymorphism and safety and efficacy of irinotecan monotherapy as the third-line treatment for advanced gastric cancer. (2019)
  • Author(s): Yamaguchi T, Iwasa S, Shoji H, Honma Y, Takashima A, Kato K, Hamaguchi T, Higuchi K, Boku N.
  • Journal Title: Gastric Cancer. Volume: 印刷中 Issue: 4 Pages: 778-784
  • DOI: 10.1007/s10120-018-00917-5
  • NAID: 40021925970
  • Peer Reviewed
• [Journal Article] Metabolomics-based Discovery of Serum Biomarkers to Predict the Side-effects of Neoadjuvant Chemoradiotherapy for Esophageal Squamous Cell Carcinoma. (2019)
  • Author(s): Nishiumi S, Fujigaki S, Kobayashi T, Kojima T, Ito Y, Daiko H, Kato K, Shoji H, Kodama Y, Honda K, Yoshida M.
  • Journal Title: Anticancer Res. Volume: 39(1) Issue: 1 Pages: 519-526
  • DOI: 10.21873/anticanres.13143
  • Peer Reviewed
• [Journal Article] Live single cell mass spectrometry reveals cancer‐specific metabolic profiles of circulating tumor cells (2019)
  • Author(s): Abouleila Yasmine、Onidani Kaoru、Ali Ahmed、Shoji Hirokazu、Kawai Takayuki、Lim Chwee Teck、Kumar Vipin、Okaya Shinobu、Kato Ken、Hiyama Eiso、Yanagida Toshio、Masujima Tsutomu、Shimizu Yoshihiro、Honda Kazufumi
  • Journal Title: Cancer Science Volume: 110 Issue: 2 Pages: 697-706
  • DOI: 10.1111/cas.13915
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] CA19-9 and apolipoprotein-A2 isoforms as detection markers for pancreatic cancer: a prospective evaluation. (2019)
  • Author(s): Honda K, Katzke VA, Hüsing A, Okaya S, Shoji H, et al.
  • Journal Title: Int J Cancer. Volume: 144（8） Issue: 8 Pages: 1877-1887
  • DOI: 10.1002/ijc.31900
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Clinical outcomes of patients with G1/G2 neuroendocrine tumors arising from foregut or hindgut treated with somatostatin analogs: a retrospective study. (2018)
  • Author(s): Ida H, Honma Y, Hirano H, Shoji H, Iwasa S, Okita N, Takashima A, Kato K, Fukuda T, Boku N.
  • Journal Title: Invest New Drugs. Volume: 印刷中 Issue: 3 Pages: 573-578
  • DOI: 10.1007/s10637-018-0669-7
  • Peer Reviewed
• [Journal Article] Retrospective Analyses of Systemic Chemotherapy and Cytoreductive Surgery for Patients with Ovarian Metastases from Colorectal Cancer: A Single-Center Experience. (2018)
  • Author(s): Sekine K, Hamaguchi T, Shoji H, Takashima A, Honma Y, Iwasa S, Kato K, Takahashi K, Kato T, Kanemitsu Y, Boku N.
  • Journal Title: Oncology. Volume: 95（4） Issue: 4 Pages: 220-228
  • DOI: 10.1159/000489665
  • Peer Reviewed
• [Journal Article] Measurement of copy number of ACTN4 to optimize the therapeutic strategy for locally advanced pancreatic cancer (2018)
  • Author(s): Shoji Hirokazu、Miura Nami、Ueno Hideki、Honda Kazufumi
  • Journal Title: Pancreatology Volume: 18 Issue: 6 Pages: 624-629
  • DOI: 10.1016/j.pan.2018.06.003
  • Peer Reviewed
• [Journal Article] A retrospective analysis of 5-fluorouracil plus cisplatin as first-line chemotherapy in the recent treatment strategy for patients with metastatic or recurrent esophageal squamous cell carcinoma. (2018)
  • Author(s): Hiramoto S, Kato K, Shoji H, Okita N, Takashima A, Honma Y, Iwasa S, Hamaguchi T, Yamada Y, Shimada Y, Boku N.
  • Journal Title: Int J Clin Oncol. Volume: 印刷中 Issue: 3 Pages: 466-472
  • DOI: 10.1007/s10147-018-1239-x
  • Peer Reviewed
• [Journal Article] Patterns of Relapse after Definitive Chemoradiotherapy in Stage II/III (Non-T4) Esophageal Squamous Cell Carcinoma. (2018)
  • Author(s): Sudo K, Kato K, Kuwabara H, Sasaki Y, Takahashi N, Shoji H, Iwasa S, Honma Y, Okita NT, Takashima A, Hamaguchi T, Yamada Y, Ito Y, Itami J, Fukuda T, Tobinai K, Boku N.
  • Journal Title: Oncology. Volume: 94（1） Issue: 1 Pages: 47-54
  • DOI: 10.1159/000480515
  • Peer Reviewed
• [Journal Article] The peripheral immune status of granulocytic myeloid-derived suppressor cells correlates the survival in advanced gastric cancer patients receiving cisplatin-based chemotherapy (2017)
  • Author(s): Shoji Hirokazu、Tada Kohei、Kitano Shigehisa、Nishimura Takashi、Shimada Yasuhiro、Nagashima Kengo、Aoki Kazunori、Hiraoka Nobuyoshi、Honma Yoshitaka、Iwasa Satoru、Takashima Atsuo、Kato Ken、Boku Narikazu、Honda Kazufumi、Yamada Tesshi、Heike Yuji、Hamaguchi Tetsuya
  • Journal Title: Oncotarget Volume: 8 Issue: 56 Pages: 95083-95094
  • DOI: 10.18632/oncotarget.18297
  • Peer Reviewed / Open Access
• [Journal Article] Clinical Outcomes of Resectable Esophageal Cancer with Supraclavicular Lymph Node Metastases Treated with Curative Intent. (2017)
  • Author(s): Honma Y, Hokamura N, Nagashima K, Sudo K, Shoji H, Iwasa S, Takashima A, Kato K, Hamaguchi T, Boku N, Umezawa R, Ito Y, Itami J, Koyanagi K, Igaki H, Tachimori Y.
  • Journal Title: Anticancer Res. Volume: 37（7） Pages: 3741-3749
  • Peer Reviewed / Open Access
• [Journal Article] Prognostic significance of gene amplification of ACTN4 in stage I and II oral tongue cancer. (2017)
  • Author(s): Kakuya T, Mori T, Yoshimoto S, Watabe Y, Miura N, Shoji H, Onidani K, Shibahara T, Honda K.
  • Journal Title: Int J Oral Maxillofac Surg. Volume: 46（8） Issue: 8 Pages: 968-976
  • DOI: 10.1016/j.ijom.2017.03.001
  • Peer Reviewed / Open Access
• [Journal Article] The peripheral immune status of granulocytic myeloid-derived suppressor cells correlates the survival in advanced gastric cancer patients receiving cisplatin-based chemotherapy. (2017)
  • Author(s): Shoji H, Tada k, Kitano S, Nishimura T, Shimada Y, Nagashima K, Aoki K, Hiraoka N, Honma Y, Iwasa S, Takashima A, Kato K, Boku N, Honda K, Yamada T, Heike Y, and Hamaguchi T.
  • Journal Title: Oncotarget. Volume: In press
  • Peer Reviewed / Open Access
• [Journal Article] Circulating tumor cellの同定と、その臨床応用 (2017)
  • Author(s): 庄司 広和、鬼谷 薫、吉本 世一、本田 一文、加藤 健
  • Journal Title: 腫瘍内科 Volume: 19(4) Pages: 422-427
• [Journal Article] A phase I study of the combination of panitumumab and bevacizumab in KRAS wild-type colorectal cancer patients previously treated with fluoropyrimidine, oxaliplatin, irinotecan and bevacizumab. (2016)
  • Author(s): Takahashi N, Iwasa S, Fukahori M, Sudo K, Sasaki Y, Shoji H, Honma Y, Okita NT, Takashima A, Hamaguchi T, Boku N, Shimada Y, Honda K, Yamada T, and Yamada Y.
  • Journal Title: Cancer Chemother Pharmacol. Volume: Sep;78(3) Issue: 3 Pages: 567-75
  • DOI: 10.1007/s00280-016-3111-x
  • Peer Reviewed
• [Journal Article] Comparison of Panitumumab Plus Irinotecan and Cetuximab Plus Irinotecan for KRAS Wild-type Metastatic Colorectal Cancer. (2016)
  • Author(s): Yamaguchi T, Iwasa S, Nagashima K, Ikezawa N, Hamaguchi T, Shoji H, Honma Y, Takashima A, Okita N, Kato K, Yamada Y, and Shimada Y.
  • Journal Title: Anticancer Res. Volume: Jul;36(7) Pages: 3531-6
  • Peer Reviewed
• [Journal Article] Serum levels of soluble programmed cell death ligand 1 as a prognostic factor on the first-line treatment of metastatic or recurrent gastric cancer. (2016)
  • Author(s): Takahashi N, Iwasa S, Sasaki Y, Shoji H, Honma Y, Takashima A, Okita NT, Kato K, Hamaguchi T, and Yamada Y.
  • Journal Title: J Cancer Res Clin Oncol. Volume: Aug;142(8) Issue: 8 Pages: 1727-38
  • DOI: 10.1007/s00432-016-2184-6
  • Peer Reviewed
• [Journal Article] Pretreatment Immune Status Correlates with Progression-Free Survival in Chemotherapy-Treated Metastatic Colorectal Cancer Patients. (2016)
  • Author(s): Tada K, Kitano S, Shoji H, Nishimura T, Shimada Y, Nagashima K, Aoki K, Hiraoka N, Honma Y, Iwasa S, Okita N, Takashima A, Kato K, Yamada Y, Katayama N, Boku N, Heike Y, Hamaguchi T.
  • Journal Title: Cancer immunology research Volume: 4(7) Issue: 7 Pages: 592-599
  • DOI: 10.1158/2326-6066.cir-15-0298
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Efficacy of adjuvant chemotherapy for non-small cell lung cancer assesed by metastatic potential assocaited with ACTN4 (2016)
  • Author(s): Miura N, Kamita M, Kakuya T, Fujiwara Y, Tsuta K, Shiraishi H, Takeshita F, Ochiya T, Hirokazu Shoji, Huang W, Ohe Y, Yamada T, Honda K
  • Journal Title: Oncotarget Volume: Apr 21 Issue: 22 Pages: 1-14
  • DOI: 10.18632/oncotarget.8890
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Prognostic role of ERBB2, MET and VEGFA expression in metastatic colorectal cancer patients treated with anti-EGFR antibodies. (2016)
  • Author(s): Takahashi N, Iwasa S, Taniguchi H, Sasaki Y, Shoji H, Honma Y, Takashima A, Okita N, Kato K, Hamaguchi T, Shimada Y, and Yamada Y.
  • Journal Title: Br J Cancer. Volume: Apr 26;114(9) Issue: 9 Pages: 1003-11
  • DOI: 10.1038/bjc.2016.74
  • Peer Reviewed / Open Access
• [Journal Article] Value of KRAS, BRAF, and PIK3CA Mutations and Survival Benefit from Systemic Chemotherapy in Colorectal Peritoneal Carcinomatosis. (2016)
  • Author(s): Sasaki Y, Hamaguchi T, Yamada Y, Takahashi N, Shoji H, Honma Y, Iwasa S, Okita N, Takashima A, Kato K, Nagai Y, Taniguchi H, Boku N, Ushijima T, and Shimada Y.
  • Journal Title: Asian Pac J Cancer Prev. Volume: 17(2) Pages: 539-43
  • Peer Reviewed / Open Access
• [Journal Article] Phase I study of a new cancer vaccine of ten mixed peptides for advanced cancer patients. (2016)
  • Author(s): Iwasa S, Yamada Y, Heike Y, Shoji H, Honma Y, Komatsu N, Matsueda S, Yamada A, Morita M, Yamaguchi R, Tanaka N, Kawahara A, Kage M, Shichijo S, Sasada T, Itoh K.
  • Journal Title: Cancer Sci. Volume: 印刷中 Issue: 5 Pages: 590-600
  • DOI: 10.1111/cas.12919
  • Peer Reviewed / Open Access
• [Journal Article] Serum level of hepatocyte growth factor is a novel marker of predicting the outcome and resistance to the treatment with trastuzumab in HER2-positive patients with metastatic gastric cancer. (2016)
  • Author(s): Takahashi N, Furuta K, Taniguchi H, Sasaki Y, Shoji H, Honma Y, Iwasa S, Okita N, Takashima A, Kato K, Hamaguchi T, Shimada Y, and Yamada Y.
  • Journal Title: Oncotarget. Volume: Jan 26;7(4) Issue: 4 Pages: 4925-38
  • DOI: 10.18632/oncotarget.6753
  • Peer Reviewed / Open Access
• [Journal Article] Phase I clinical trial of oral administration of S-1 in combination with intravenous gemcitabine and cisplatin in patients with advanced biliary tract cancer. (2016)
  • Author(s): Shoji H, Morizane C, Sakamoto Y, Kondo S, Ueno H, Takahashi H, Ohno I, Shimizu S, Mitsunaga S, Ikeda M, Okusaka T.
  • Journal Title: Japanese journal of clinical oncology Volume: 46 Pages: 132-137
  • DOI: 10.1093/jjco/hyv179
  • Peer Reviewed / Open Access
• [Journal Article] 血液apolipoprotein-A2 isoforms による早期膵がんの診断 (2016)
  • Author(s): 鬼谷 薫、庄司 広和、本田 一文
  • Journal Title: がん分子標的治療 Volume: 14(4) Pages: 108-113
• [Presentation] The hyperprogressive disease during nivolumab treatment or irinotecan treatment in patients with advanced gastric cancer. (2019)
  • Author(s): Aoki M, Shoji H, Imazeki H, Miyamoto T, Hirano H, Honma Y, Iwasa S, Okita N, Takashima A, Kato K, Boku N.
  • Organizer: 2019 ASCO Gastrointestinal Cancers Symposium
  • Int'l Joint Research
• [Presentation] Survival impact of the response at 12 weeks in patients with advanced gastric cancer received firstline chemotherapy. (2019)
  • Author(s): Arakaki M, Aoki M, Imazeki H, Shoji H, Honma Y, Iwasa S, Okita N,Takashima A, Kato K, Boku N.
  • Organizer: 2019 ASCO Gastrointestinal Cancers Symposium
  • Int'l Joint Research
• [Presentation] Phase 1/2 study of ramucirumab plus nivolumab in patients in second line treatment for advanced gastric adenocarcinoma (NivoRam study). (2019)
  • Author(s): Hara H, Shoji H, Takahari D, Esaki T, Machida N, Nagashima K, Aoki K, Honda K, Miyamoto T, Boku N, Kato K.
  • Organizer: 2019 ASCO Gastrointestinal Cancers Symposium
  • Int'l Joint Research
• [Presentation] Preliminary result of phase 1/2 study of ramucirumab plus nivolumab in patients with previously treated advanced gastric adenocarcinoma (NivoRam study) (2018)
  • Author(s): Takahari D, Shoji H, Hara H, Esaki T, Machida N, Nagashima K, Aoki K, Honda K, Miyamoto T, Boku N, Kato K.
  • Organizer: 2018 ASCO annual meeting
  • Int'l Joint Research
• [Presentation] 次世代シーケンサーによる血中循環腫瘍細胞(CTCs)および血中腫瘍循環DNA(ctDNA)のリアルタイムモニタリング (2018)
  • Author(s): 鬼谷薫、庄司広和、吉本世一、三浦奈美、柴原孝彦、加藤健、本田一文
  • Organizer: 日本分子腫瘍マーカー研究会
• [Presentation] Expression of B7-H3 (CD276) in surgically resected esophageal squamous cell carcinoma (2018)
  • Author(s): Maruki Y, Takashima A, Miyamoto T, Hirano H, Shoji H, Honma Y, Iwasa S, Okita N, Kato K, Sekine S, Koyanagi K, Daiko H, Kitano S, Aoki K, Boku N
  • Organizer: American Society of Clinical Oncology 2018 Gastrointesinal Cancer Symposium
  • Int'l Joint Research
• [Presentation] A phase 1/2 study of ramucirumab plus nivolumab in patients with previously treated advanced gastric adenocarcinoma. (2017)
  • Author(s): Shoji H, Miyamoto H, Takahari D, Hara H, Machida N, Esaki T, Nagashima K, Aoki K, Honda K, Nagata Y, Miyamoto T, Boku N, Kato K.
  • Organizer: European Society for Medical Oncology 2017 Congress
  • Int'l Joint Research
• [Presentation] Next-generation sequencing of circulating tumor cells isolated from peripheral blood of patients with head and neck or gastrointestinal cancer. (2017)
  • Author(s): Onidani K, Yoshimoto S, Miura N, Shoji H, Kato K, Shibahara T, Honda K.
  • Organizer: European Society for Medical Oncology 2017 Congress Asia 2017
  • Int'l Joint Research
• [Presentation] Possibility of a novel molecular therapeutic target for tongue cancer. (2017)
  • Author(s): Onidani K, Kakuya T, Watabe Y, Miura N, Shoji H, Shibahara T, Honda K.
  • Organizer: Human Proteome Organisation World Congress 2017
  • Int'l Joint Research
• [Presentation] Evaluation of the safety and efficacy of combined the KM-CART and chemotherapy for gastrointestinal cancers with massive ascites. (2017)
  • Author(s): Y. Nagata, K. Kato, H. Matsushita, T. Yamaguchi, T. Miyamoto, H. Shoji, S. Iwasa, Y. Honma, A. Takashima, T. Hamaguchi, M. Saruta, N. Boku
  • Organizer: European Society for Medical Oncology 2017 Congress Asia 2017
  • Int'l Joint Research
• [Presentation] A phase 1/2 study of ramucirumab plus nivolumab in patients with previously treated advanced gastric adenocarcinoma. (2017)
  • Author(s): Shoji H, Miyamoto H, Takahari D, Hara H, Machida N, Esaki T, Nagashima K, Aoki K, Honda K, Nagata Y, Miyamoto T, Boku N, Kato K.
  • Organizer: 日本臨床腫瘍学会学術集会
• [Presentation] Prognostic significance of gene amplification of ACTN4 in stage I and II oral tongue cancer. (2017)
  • Author(s): Onidani K, Kakuya T, Miura N, Shoji H, Shibahara T, Honda K.
  • Organizer: 日本癌学会学術総会
• [Presentation] 次世代シーケンサーによる血中循環腫瘍細胞(CTCs)の遺伝子変異プロファイリング (2017)
  • Author(s): 鬼谷 薫、吉本世一、三浦奈美、庄司広和、加藤 健、柴原孝彦、本田一文
  • Organizer: 日本分子腫瘍マーカー研究会
• [Presentation] Next-generation sequencing of circulating tumor cells isolated from peripheral blood of patients with head and neck or gastrointestinal cancer (2016)
  • Author(s): H.Shoji, K.Kato, S.Yoshimoto, F.Kakizaki, K.Furuta, K.Onidani, N.Miura, K.Honda.
  • Organizer: ESMO 2016 Congress
  • Place of Presentation: Copenhagen, Denmark
  • Year and Date: 2016-10-07
  • Int'l Joint Research
• [Presentation] Assessment of efficacy of adjuvant chemotherapy for non-small cell lung cancer with metastatic ability involving ACTN4 (2016)
  • Author(s): K.Honda, N.Miura, H.Shiraishi, K.Onidani, H.Shoji, T.Yamada, Y.Fujiwara, Y.Ohe
  • Organizer: ESMO 2016 Congress
  • Place of Presentation: Copenhagen, Denmark
  • Year and Date: 2016-10-07
  • Int'l Joint Research