Establishment of cancer therapytargeted for DNA dependent protein kinase and investigation of its predictive factor

• Project/Area Number: 22501031
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Tumor diagnosis
• Research Institution: Saga University
• Principal Investigator: ARAGANE Naoko 佐賀大学, 医学部, 講師 (20321846)
• Co-Investigator(Kenkyū-buntansha): SUEOKA Eizaburo 佐賀大学, 医学部, 准教授 (00270603) ; IWANAGA Kentaro 佐賀大学, 医学部, 客員研究員 (60380755)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: バイオマーカー / 肺癌 / DNA依存性キナーゼ / トポイソメラーゼIIα / DNA二重鎖切断 / 成人T細胞性白血病

Research Abstract

NK314, a dual inhibitor of DNA dependent protein kinase (DNA-PK) and topoisomerase IIαpotently inhibited cell growth of adult T cell leukemia and lung cancer cell lines. The inhibitory effect was mediated through enhancement of DNA double strand breaks and prolonged inhibitory effect ofDNA repair. As for the predictive factors for DNA-PK inhibitors, protein level of hnRNP B1, an RNA binding protein, was strongly associated with that of DNA-PKcs. However, the inhibitory effect of cell growth of lung cancer cells was not statistically associated with protein levels of DNA-PKcs nor hnRNP B1. Further investigation for seeking the predictive factors would be needed.

Research Products

• [Journal Article] NK314 potentiates anti-tumor activity with adult T-cell leukemia-lymphoma cells by inhibition of dual targets on topoisomerase Iiαand DNA-dependent protein kinase (2011)
  • Author(s): Hisatomi T,Sueoka-Aragane N,Sato A,Tomimasu R, Ide M, Kurimasa A,Okamoto K, Kimura S,Sueoka E.
  • Journal Title: Blood Volume: 117 Pages: 3575-84
  • Peer Reviewed
• [Journal Article] NK314 potentiates anti-tumor activity with adult T-cell leukemia-lymphoma cells by inhibition of dual targets on topoisomerase IIα and DNA-dependent protein kinase (2011)
  • Author(s): Hisatomi T, Sueoka-Aragane N, et al
  • Journal Title: Blood Volume: 117 Pages: 3575-3584
  • Peer Reviewed
• [Presentation] DNA dependent protein kinase as a new molecular target for treatment of non-small cell lung cancer (2012)
  • Author(s): Naoko Sueoka-Aragane, Akemi Sato,Kentaro Iwanaga, Naomi Kobayashi,Shinya Kimura,Eisaburo Sueoka
  • Organizer: American Association for Cancer Research
• [Presentation] Dual targeting therapy on topoisomerase IIa and DNA-dependent protein kinase is a promising strategy for adult T cell leukemia-lymphoma. (2012)
  • Author(s): Takashi Hisatomi,Naoko Aragane,Akemi Sato, Masaru Ide, Kazuya Okamoto, Shinya Kimura, Eisaburo Sueoka
  • Organizer: The 10th Japan-Korea Joint symposium on Cancer and Ageing Research
• [Presentation] The role of hypoxia inducible factors on maintenance of hematopoietic stem cells and leukemogenesis (2012)
  • Author(s): Sueoka E,Ide M,Sueoka-Aragane N, SatoA,Nakamura H, Sotomaru Y, Taya C, Yonekawa H,Nakachi K,Kubota Y,Kimura S,Tanimoto K
  • Organizer: 2012 Tumor Microenvironment GCRC International Symposium
  • Place of Presentation: Seoul
• [Presentation] Taylor made treatment using monitoring biomarkers for acquired resistance to molecular targeted therapy (2012)
  • Author(s): 荒金 尚子
  • Organizer: 2012 Tumor Microenvironment GCRC International Symposium
  • Place of Presentation: 韓国ソウル
• [Presentation] 耐性原因マーカーのモニタリングによるテイラーメイド治療 (2012)
  • Author(s): 荒金 尚子 et al
  • Organizer: 第16回日本がん分子標的治療学会.
  • Place of Presentation: 福岡
• [Presentation] DNA dependent protein kinase as a new molecular target for treatment of non-small cell lung cancer (2012)
  • Author(s): 荒金尚子, et al
  • Organizer: American Association for Cancer Research
  • Place of Presentation: 米国シカゴ
• [Presentation] Dual targeting therapy on topoisomerase IIα and DNA-dependent protein kinase is a promising strategy for adult T-cell leukemia-lymphom (2012)
  • Author(s): 久富崇、荒金尚子, et al
  • Organizer: The 10th Korea-Japan Joint Symposium on Cancer and Aging Research
  • Place of Presentation: 東京
• [Presentation] Shinya Kimura Overexpression of hnRNP B1 inhibits DNA repair by interaction with DNA-dependent protein kinase complex in adult T-cell leukemia. (2011)
  • Author(s): Eisaburo Sueoka, Takashi Hisatomi, Naoko Sueoka-Aragane, Akemi Sato, Rika Tomimasu, Masaru Ide2
  • Organizer: The XXV Symposium of the International Association for Comparative Research on Leukemia and Related Diseases
  • Year and Date: 2011-09-17
• [Presentation] DNA-dependent protein kinase as a promising molecular target for the treatment of adult T-cell leukemia-lymphoma (2011)
  • Author(s): Takashi Hisatomi, Naoko Sueoka-Aragane, Akemi Sato, Rika Tomimasu, Masaru Ide, Shinya Kimura and Eisaburo Sueoka
  • Organizer: ヨーロッパ血液学会
  • Place of Presentation: ロンドン(英国)
• [Presentation] DNA-dependent protein kinase as a promising molecular target for the treatment of adult T-cell leukemia-lymphoma (2011)
  • Author(s): 久富崇、荒金尚子, et al
  • Organizer: ヨーロッパ血液学会
  • Place of Presentation: 英国ロンドン
• [Presentation] DNA dependent protein kinase as a new molecular target for treatment of non-small cell lung cancer (2011)
  • Author(s): 末岡栄三朗、荒金尚子, et al
  • Organizer: The XXV Symposium of the International Association for Comparative Research on Leukemia and Related Diseases
  • Place of Presentation: 東京
• [Presentation] DNA-dependent protein kinase as a molecular target of chemotherapy on hematological malignancy. (2010)
  • Author(s): 末岡 栄三朗
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2010-12-10