Evaluation of TYRO3 as a therapeutic target in breast and lung cancers

• Project/Area Number: 26460627
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Applied pharmacology
• Research Institution: Kobe University
• Principal Investigator: Minami Hironobu 神戸大学, 医学研究科, 教授 (60450574)
• Co-Investigator(Kenkyū-buntansha): 高尾 信太郎 神戸大学, 医学研究科, 客員教授 (10717218) ; 伊藤 智雄 神戸大学, 医学部附属病院, 教授 (20301880) ; 眞庭 謙昌 神戸大学, 医学研究科, 教授 (50362778)
• 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: ¥260,000 (Direct Cost: ¥200,000、Indirect Cost: ¥60,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
• Keywords: 乳癌 / 肺癌 / TYRO3 / Gas6 / 乳がん / 肺がん / Tyro3 / PDX

Outline of Final Research Achievements

The expression of TYRO3 and Gas6 was investigated using RNA in situ hybridization in clinical tumor samples of breast and lung cancers. Both TYRO3 and Gas6 was highly expressed in luminal A breast cancer cells, but not in luminal B type or triple negative breast cancer. HER2-positive breast cancer expressed no or weak expression. These results support our hypothesis that inhibition of TYRO3 can be a therapeutic strategy for hormone receptor-positive breast cancer.
TYRO3 was expressed in some of lung cancers, but no apparent relationship was observed between the expression of TYRO3 and EGFR mutations or ALK status.

Research Products

• [Journal Article] A prospective study of the antiemetic effect of palonosetron in malignant lymphoma patients treated with the CHOP regimen. (2016)
  • Author(s): Miyata Y, Yakushijin K, Inui Y, Imamura Y, Goto H, Mizutani Y, Kurata K, Kakiuchi S, Sanada Y, Minami Y, Kawamoto S, Yamamoto K, Ito M, Tominaga R, Gomyo H, Mizuno I, Nomura T, Kitagawa K, Sugimoto T, Murayama T, Matsuoka H, Minami H.
  • Journal Title: Int J Hematol Volume: 104 Issue: 6 Pages: 682-691
  • DOI: 10.1007/s12185-016-2089-9
  • Peer Reviewed
• [Journal Article] A phase 1, multicenter, open-label, 2-group, parallel, dose-escalation study of oral sonidegib in Asian patients with advanced solid tumors. (2016)
  • Author(s): Minami H, Ando Y, Ma BBY, Lee J-H, Momota H, Fujiwara Y, Li L, Fukino K, Ito K, Tajima T, Mori A, Lin C-C.
  • Journal Title: Cancer Science Volume: 107 Issue: 10 Pages: 1477-1483
  • DOI: 10.1111/cas.13022
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] The comobination of HLA-B*15:01 and DRB1*15:01 is associated with gemcitabine plus erlotinib-induced interstitial lung disease in pateints with advanced pancreatic cancer. (2016)
  • Author(s): Nishimura M, Toyoda M, Tkenaka K, Imamura Y, Chayahara N, Kiyota N, Mukohara T, Kotake T, Tsuji A, Saito K, Saito Y, Minami H.
  • Journal Title: Cancer Chemother Pharmacol Volume: 77 Issue: 6 Pages: 1165-1171
  • DOI: 10.1007/s00280-016-3026-6
  • Peer Reviewed
• [Journal Article] A sensitive cytometry based system for enumeration, capture and analysis of gene mutations of circulating tumor cells. (2016)
  • Author(s): Sawada T, Watanabe M, Fujimura Y, Yagishita S, Yashita S, Shimoyama T, Maeda Y, Kanda S, Yunokawa M, Tamura K, Tamura T, Minami H, Koh Y, Koizumi F.
  • Journal Title: Cancer Sci Volume: 107 Issue: 3 Pages: 307-314
  • DOI: 10.1111/cas.12868
• [Journal Article] Validity of new methods to evaluate renal function in cancer patients treated with cisplatin. (2016)
  • Author(s): Funakoshi Y, Fujiwara Y, Kiyota N, Mukohara T, Shimada T, Toyoda M, Imamura Y, Chayahara N, Tomioka H, Umezu M, Otsuki N, Nibu K, Minami H
  • Journal Title: Cancer Chemother Pharmacol Volume: 77 Issue: 2 Pages: 281-288
  • DOI: 10.1007/s00280-016-2966-1
• [Journal Article] Comparison of 2D- and 3D-culture models as drug-testing platforms in breast cancer (2015)
  • Author(s): Imamura Y, Mukohara T, Shimono Y, Funakoshi Y, Chayahara N, Toyoda M, Kiyota N, Takao S, Kono S, Nakatsura T, Minami H
  • Journal Title: Oncol Rep Volume: 33 Issue: 4 Pages: 1837-1843
  • DOI: 10.3892/or.2015.3767
  • NAID: 120005758024
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] MicroRNA regulation of human breast cancer stem cells (2015)
  • Author(s): 194.Shimono Y, Mukoyama J, Nakamura S, Minami H.
  • Journal Title: J Clin Med Volume: 5 Issue: 1 Pages: 2-2
  • DOI: 10.3390/jcm5010002
  • NAID: 120005697222
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] TYRO3 as a potential therapeutic target in breast cancer. (2014)
  • Author(s): Ekyalongo RC, Mukohara T, Funakoshi Y, Tomioka H, Kataoka Y, Shimono Y, Chayahara n, Toyada M, Kiyota N, Minami H
  • Journal Title: Anticancer Res Volume: 34 Pages: 3337-45
• [Presentation] MicroRNA-mediated upregulation of the WNT signaling activities in human breast cancer stem cells (2017)
  • Author(s): 113. Shimono Y, Isobe T, Turtoi A, Mukohyama J, Mukohara T, Suzuki A, Castronovo V, Minami H.
  • Organizer: American Association for Cancer Research
  • Place of Presentation: Washington DC (USA)
  • Year and Date: 2017-04-01
  • Int'l Joint Research
• [Presentation] MicroRNA-7 suppresses RB1 expression leading to chromosomal instability in leukemia cells harboring c-Kit mutation. (2017)
  • Author(s): 112. Kurata K, Kawamoto S, Masutani R, Yakushijin K, Yamamoto K, Matsuoka H, Takubo T, Minami H.
  • Organizer: American Association for Cancer Research
  • Place of Presentation: Washington DC (USA)
  • Year and Date: 2017-04-01
  • Int'l Joint Research
• [Presentation] 3D culture may better represent trastuzumab resistance associated with PIK3CA mutation than 2D culture. (2017)
  • Author(s): 115. Tatara T, Mukohara T, Tanaka R, Shimono Y, Toyoda M, Kiyota N, Hirai M, Kakeji Y, Minami H.
  • Organizer: American Association for Cancer Research
  • Place of Presentation: Washington DC
  • Year and Date: 2017-04-01
  • Int'l Joint Research
• [Presentation] Quantitative mass spectrometry imaging of erlotinib in skin rashed of cancer patients receiving erlotinib (2017)
  • Author(s): 114. Nishimura M, Aikawa H, Hayashi M, Mizutani Y, Takenaka K, Imamura Y, Chayahara N, Toyoda M, Kiyota N, Mukohara T, Hamada A, Minami H.
  • Organizer: American Association for Cancer Research
  • Place of Presentation: Washington DC (USA)
  • Year and Date: 2017-04-01
  • Int'l Joint Research
• [Presentation] Comparison of 2D- and 3D-culture models as drug-testing platforms in breast cancer (2015)
  • Author(s): 107. Imamura Y, Mukohara T, Shimono Y, Funakoshi Y, Chayahara N, Toyoda M, Kiyota N, Takao S, Kono S, Nakatsura T, Minami H
  • Organizer: Am Assoc Cancer Res
  • Place of Presentation: Philadelphia
  • Year and Date: 2015-04-18
  • Int'l Joint Research
• [Presentation] Comparison of 2D- and 3D-culture models as drug-testing platforms in breast cancer (2015)
  • Author(s): Yoshinori Imamura, Toru Mukohara, Yohei Shimono, Yohei Funakoshi, Naoko Chayahara, Masanori Toyoda, Naomi Kiyota, Shintaro Takao, Seishi Kono, Tetsuya Nakatsura, and Hironobu Minami
  • Organizer: AACR Annual Meeting 2015
  • Place of Presentation: Philadelphia
  • Year and Date: 2015-04-17 – 2015-04-20
• [Presentation] Clinicopathological Analysis of Salivary Duct Carcinoma and Salivary Gland Adenocarcinoma (2014)
  • Author(s): 今村 善宣、清田 尚臣、大月 直樹、平井 千穂子、伊藤 智雄、船越 洋平、佐々木 良平、丹生 健一、向原 徹、南 博信
  • Organizer: 第12回日本臨床腫瘍学会学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2014-07-17 – 2014-07-19