Development of novel microRNA-based therapy against KRAS/BRAF-mutant colorectal cancer

• Project/Area Number: 25462057
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Okayama University
• Principal Investigator: TAZAWA HIROSHI 岡山大学, 大学病院, 助教 (90415513)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: マイクロRNA / 大腸癌 / KRAS / BRAF / EGFR

Outline of Final Research Achievements

KRAS/BRAF-mutant colorectal cancer is an intractable disease that frequently shows the refractory to chemotherapy, recurrence and metastatic progression. Since EGFR signaling pathway is constitutively activated in KRAS/BRAF-mutant colorectal cancer, the development of novel therapy for strongly suppressing EGFR signaling pathway is important issue. Here we show that oncolytic adenoviruses have profound antitumor effect through activation of EGFR-suppressive microRNA and induction of apoptosis- and autophagy-related cell death against KRAS/BRAF-mutant colorectal cancer.

Research Products

• [Journal Article] Biological ablation of sentinel lymph node metastasis in submucosally invaded early gastrointestinal cancer (2015)
  • Author(s): Kikuchi S, et al.
  • Journal Title: Mol Ther Volume: 23 Pages: 501-509
  • DOI: 10.1038/mt.2014.244
  • NAID: 120005537574
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Fluorescence virus-guided capturing system of human colorectal circulating tumour cells for non-invasive companion diagnostics. (2015)
  • Author(s): Kikuchi S, Kishimoto H, Tazawa H, Hashimoto Y, Kuroda S, Nishizaki M, Nagasaka T, Shirakawa Y, Kagawa S, Urata Y, Hoffman RM, Fujiwara T.
  • Journal Title: Gut Volume: 23(3) Pages: 501-509
  • DOI: 10.1136/gutjnl-2014-306957
  • NAID: 120005526615
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Viral transduction of HER2-extracellular domain expands trastuzumab-based photoimmunotherapy for HER2 negative breast cancer cells (2015)
  • Author(s): Shimoyama K, Kagawa S, Ishida M, Watanabe S, Noma K, Takehara K, Tazawa H, Hashimoto Y, Tanabe S, Matsuoka J, Kobayashi H, Fujiwara T
  • Journal Title: Breast Cancer Res Treat Volume: 149 Pages: 597-605
  • DOI: 10.1007/s10549-015-3265-y
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Cancer cells mimic in vivo spatial-temporal cell-cycle phase distribution and chemosensitivity in 3-dimensional gelfoam histoculture but not 2-dimensional culture as visualized with real-time FUCCI imaging (2015)
  • Author(s): Yano S, Miwa S, Mii S, Hiroshima Y, Uehara F, Kishimoto H, Tazawa H, Zhao M, Bouvet M, Fujiwara T, Hoffman RM
  • Journal Title: Cell Cycle Volume: 14 Pages: 808-819
  • DOI: 10.1080/15384101.2014.1000685
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Experimental curative fluorescence-guided surgery of highly invasive glioblastoma multiforme selectively labeled with killer-reporter adenovirus. (2015)
  • Author(s): Yano S, Miwa S, Kishimoto H, Toneri M, Hiroshima Y, Yamamoto M, Bouvet M, Urata Y, Tazawa H, Kagawa S, Fujiwara T, Hoffman RM
  • Journal Title: Molecular Therapy Volume: 23 Pages: 1182-1188
  • DOI: 10.1038/mt.2015.63
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Targeting tumors with a killer-reporter adenovirus for curative fluorescence-guided surgery of soft-tissue sarcoma (2015)
  • Author(s): Yano S, Miwa S, Kishimoto H, Uehara F, Tazawa H, Toneri M, Hiroshima Y, Yamamoto M, Urata Y, Kagawa S, Bouvet M, Fujiwara T
  • Journal Title: Oncotarget Volume: 6 Pages: 13133-13148
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Color-coding cancer and stromal cells with genetic reporters in a patient-derived orthotopic xenograft (PDOX) model of pancreatic cancer enhances fluorescence-guided surgery (2015)
  • Author(s): Yano S, Hiroshima Y, Maawy A, Kishimoto H, Suetsugu A, Miwa S, Toneri M, Yamamoto M, Katz MH, Fleming JB, Urata Y, Tazawa H, Kagawa S, Bouvet M, Fujiwara T, Hoffman RM.
  • Journal Title: Cancer Gene Therapy Volume: 22 Pages: 344-350
  • DOI: 10.1038/cgt.2015.26
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Genetic and epigenetic alterations of netrin-1 receptors in gastric cancer with chromosomal instability (2015)
  • Author(s): Toda K, Nagasaka T, Umeda Y, Tanaka T, Kawai T, Fuji T, Taniguchi F, Yasui K, Kubota N, Takehara Y, Tazawa H, Kagawa S, Sun DS, Nishida N, Goel A, Fujiwara T.
  • Journal Title: Clin Epigenetics. Volume: 7 Pages: 73-73
  • DOI: 10.1186/s13148-015-0096-y
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Invading cancer cells are predominantly in G0/G1 resulting in chemoresistance demonstrated by real-time FUCCI imaging (2014)
  • Author(s): Yano S, Miwa S, Mii S, Hiroshima Y, Uehara F, Yamamoto M, Kishimoto H, Tazawa H, Bouvet M, Fujiwara T, Hoffman RM
  • Journal Title: Cell Cycle Volume: 13 Pages: 953-960
  • DOI: 10.4161/cc.27818
  • Peer Reviewed
• [Journal Article] Chronic inflammation-derived nitric oxide converts human colonic adenoma cells into adenocarcinoma cells (2013)
  • Author(s): Tazawa H, Kawaguchi T, Kobayashi T, Kuramitsu Y, Wada S, Satomi Y, Nishino H, Kobayashi M, Kanda Y, Osaki M, Kitagawa T, Hosokawa M and Okada F
  • Journal Title: Experimental Cell Research Volume: 319 Pages: 2835-2844
  • DOI: 10.1016/j.yexcr.2013.08.006
  • Peer Reviewed
• [Journal Article] A genetically engineered oncolytic adenovirus decoys and lethally traps quiescent human cancer stem-like cells into S/G2/M-phases (2013)
  • Author(s): Yano S, Tazawa H, Hashimoto Y, Shirakawa Y, Kuroda S, Nishizaki M, Kishimoto H, Uno F, Nagasaka T, Urata Y, Kagawa S, Hoffman RM, Fujiwara T
  • Journal Title: Clinical Cancer Research Volume: 19 Pages: 6495-6505
  • DOI: 10.1158/1078-0432.ccr-13-0742
  • Peer Reviewed
• [Journal Article] A novel synergistic effect of iron depletion on antiangiogenic cancer therapy. (2013)
  • Author(s): Tazawa H, Kagawa S, Fujiwara T
  • Journal Title: Expert Opinion on Biological Therapy Volume: 13 Pages: 1569-1583
  • DOI: 10.1517/14712598.2013.845662
  • Peer Reviewed
• [Journal Article] Oncolytic adenovirus-induced autophagy: tumor-suppressive effect and molecular basis (2013)
  • Author(s): Tazawa H, Kagawa S, Fujiwara T
  • Journal Title: Acta Medica Okayama Volume: 67 Pages: 333-342
  • NAID: 120005353344
  • Peer Reviewed
• [Presentation] KRAS/BRAF変異を持つ大腸癌に対する新たな腫瘍融解ウイルス療法の開発 (2015)
  • Author(s): 田村周太、田澤 大、堀 直人、國府島 健、菊地覚次、黒田新士、岸本浩行、永坂岳司、西崎正彦、浦田泰生、香川俊輔、藤原俊義
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-10-08
• [Presentation] Preclinical evaluation of tumor-specific oncolytic virotherapy against human colorectal cancer cells with different KRAS/BRAF mutation and microsatellite stability (2015)
  • Author(s): Tamura S, Tazawa H, Hori N, Koujima T, Kikuchi S, Kuroda S, Kishimoto H, Nagasaka T, Nishizaki M, Urata Y, Kagawa S, Fujiwara T
  • Organizer: 第21回日本遺伝子治療学会
  • Place of Presentation: 大阪
  • Year and Date: 2015-07-24
• [Presentation] Companion diagnostics-based telomerase-specific oncolytic virotherapy: preclinical evaluation in human colorectal cancer cell lines differentially affected in the RAS/RAF/MEK signaling pathway (2015)
  • Author(s): Tamura S, Tazawa H, Hori N, Koujima T, Kikuchi S, Kuroda S, Kishimoto H, Nagasaka T, Nishizaki M, Urata Y, Kagawa S, Fujiwara T
  • Organizer: 106th Annual Meeting of the American Association for Cancer Research
  • Place of Presentation: Philadelphia, USA
  • Year and Date: 2015-04-18
  • Int'l Joint Research
• [Presentation] Cytotoxic effect of photosensitive fluorescent protein KillerRed-expressing adenovirus against human cancer cells (2013)
  • Author(s): Takehara K, Tazawa H, Hashimoto Y, Kishimoto H, Narii N, Mizuguchi H, Fujiwara T
  • Organizer: 104th Annual Meeting of the American Association for Cancer Research
  • Place of Presentation: Washington DC, USA
• [Presentation] Telomerase-specific oncolytic adenovirus OBP-301 kills quiescent peritonially disseminated cancer cells (2013)
  • Author(s): Yano S, Tazawa H, Kishimoto H, Fujiwara T, Hoffman RM
  • Organizer: 104th Annual Meeting of the American Association for Cancer Research
  • Place of Presentation: Washington DC, USA
• [Presentation] A novel adenovirus-based CTC detection technique and its clinical applications (2013)
  • Author(s): Tazawa H, Takakura M, Katagiri N
  • Organizer: 第19回日本遺伝子治療学会
  • Place of Presentation: 岡山
• [Presentation] A novel apoptotic mechanism of genetically engineered adenovirus-mediated tumor-specific p53 overexpression through E1A-dependent p21 and MDM2 suppression (2013)
  • Author(s): Tazawa H, Yamasaki Y, Hashimoto Y, Kuroda S, Yano S, Yoshida R, Uno F, Mizuguchi H, Ohtsuru A, Urata Y, Kagawa S, Fujiwara T
  • Organizer: 第19回日本遺伝子治療学会
  • Place of Presentation: 岡山
• [Presentation] 腫瘍融解ウイルス療法におけるE2F1誘導性マイクロRNAの腫瘍抑制的機能 (2013)
  • Author(s): 田澤 大、長谷井 嬢、大西哲平、矢野修也、香川俊輔、藤原俊義
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜
• [Book] Tumor Suppressor Genes: Functions, Regulation and Health Effects (2013)
  • Author(s): Tazawa H, Kagawa S, Fujiwara T
  • Total Pages: 373
  • Publisher: Nova Science Publishers