Identification of anti-cancer targets based on synthetic lethality between paralogous genes

2013 Fiscal Year Final Research Report

• Project/Area Number: 23701110
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Clinical oncology
• Research Institution: National Center of Neurology and Psychiatry
• Principal Investigator: OGIWARA Hideaki 独立行政法人国立がん研究センター, 研究所, 研究員 (40568953)
• Project Period (FY): 2011 – 2013
• Keywords: SWI/SNF / BRG1 / 合成致死 / クロマチンリモデリング / 分子標的治療

Research Abstract

BRG1 gene is mutated or lost in 10% of lung adenocarcinoma. We found that BRM, BRG1 paralogous gene, is essential for BRG1 deficient cancer cells, that is, BRM is synthetically lethal with BRG1. Our research indicated that molecular target inhibitor for BRM is a candidate of anti-cancer agent for the cancer patient with BRG1 deficiency. Now, we started the development of BRM inhibitor to lead to translational research.

Research Products

• [Journal Article] SWI/SNF Factors Required for Cellular Resistance to DNA Damage Include ARID1A and ARID1B and Show Interdependent Protein Stability (2014)
  • Author(s): Watanabe R, Ui A, Kanno S, Ogiwara H, Nagase T, Kohno T, Yasui A
  • Journal Title: Cancer Res. Volume: 74 Pages: 2465-2475
  • Peer Reviewed
• [Journal Article] C646, a selective small molecule inhibitor of histone acetyltransferase p300, radiosensitizes lung cancer cells by enhancing mitotic catastrophe (2014)
  • Author(s): Oike T, Komachi M, Ogiwara H, Amornwichet N, Saitoh Y, Torikai K, Kubo N, Nakano T, Kohno T
  • Journal Title: Radiother Oncol. Volume: (In press)
  • Peer Reviewed
• [Journal Article] Druggable Oncogene Fusions in Invasive Mucinous Lung Adenocarcinoma (2014)
  • Author(s): Nakaoku T, Tsuta K, Ichikawa H, Shiraishi K, Sakamoto H, Enari M, Furuta K, Shimada Y, Ogiwara H, Watanabe SI, Nokihara H, Yasuda K, Hiramoto M, Nammo T, Ishigame T, Schetter AJ, Okayama H, Harris CC, Kim YH, Mishima M, Yokota J, Yoshida T, Kohno T
  • Journal Title: Clin Cancer Res. Volume: (In press)
  • Peer Reviewed
• [Journal Article] Fine-tuning of DNA damage-dependent ubiquitination by OTUB2 supports the DNA repair pathway choice (2014)
  • Author(s): Kato K, Nakajima K, Ui A, Muto-Terao Y, Ogiwara H, Nakada S
  • Journal Title: Mol Cell. Volume: 53 Pages: 617-630
  • Peer Reviewed
• [Journal Article] Molecular Mechanisms Underlying Oncogenic RET Fusion in Lung Adenocarcinoma (2014)
  • Author(s): Mizukami T, Shiraishi K, Shimada Y, Ogiwara H, Tsuta K, Ichikawa H, Sakamoto H, Kato M, Shibata T, Nakano T, Kohno T
  • Journal Title: J Thorac Oncol. Volume: 9 Pages: 622-630
  • Peer Reviewed
• [Journal Article] Chromatin-regulating proteins as targets for cancer therapy (2014)
  • Author(s): Oike T, Ogiwara H, Amornwichet N, Nakano T, Kohno T
  • Journal Title: J Radiat Res. Volume: (In press)
  • Peer Reviewed
• [Journal Article] Possible involvement of LKB1-AMPK signaling in non-homologous end joining (2014)
  • Author(s): Ui A, Ogiwara H, Nakajima S, Kanno S, Watanabe R, Harata M, Okayama H, Harris CC, Yokota J, Yasui A, Kohno T
  • Journal Title: Oncogene. Volume: 33 Pages: 1640-1648
  • Peer Reviewed
• [Journal Article] Inactivating mutations in SWI/SNF chromatin remodeling genes in human cancer (2013)
  • Author(s): Oike T, Ogiwara H, Nakano T, Yokota J, Kohno T
  • Journal Title: Jpn J Clin Oncol. Volume: 43 Pages: 849-855
  • Peer Reviewed
• [Journal Article] Curcumin suppresses multiple DNA damage response pathways and has potency as a sensitizer to PARP inhibitor (2013)
  • Author(s): Ogiwara H, Ui A, Shiotani B, Zou L, Yasui A, Kohno T
  • Journal Title: Carcinogenesis. Volume: 34 Pages: 2486-2497
  • Peer Reviewed
• [Journal Article] A synthetic lethality-based strategy to treat cancers harboring a genetic deficiency in the chromatin remodeling factor BRG1 (2013)
  • Author(s): Oike T, Ogiwara H, Tominaga Y, Ito K, Ando O, Tsuta K, Mizukami T, Shimada Y, Isomura H, Komachi M, Furuta K, Watanabe S, Nakano T, Yokota J, Kohno T
  • Journal Title: Cancer Res. Volume: 73 Pages: 5508-5518
  • Peer Reviewed
• [Presentation] Personalized Medicine of Lung Adenocarcinoma Based on Genetic Alterations (2013)
  • Author(s): Takashi Kohno Ph D, Hideaki Ogiwara Ph D, Tatsuji Mizukami MD
  • Organizer: 原研・国際キックオフシンポジウム
  • Year and Date: 2013-11-28
• [Presentation] DNA切断修復と発がん・がん治療 (2013)
  • Author(s): 河野隆志、荻原秀明、尾池貴洋、水上達治、白石航也
  • Organizer: 日本放射線影響学会第56回大会
  • Year and Date: 2013-10-19
• [Presentation] Curcumin suppresses multiple DNA damage response pathways and has potency as sensitizer to PARP inhibitor (2013)
  • Author(s): Hideaki Ogiwara, Ayako Ui, Bunsho Shiotani, Lee Zou, Akira Yasui, Takashi Kohno
  • Organizer: 第72回日本癌学会学術総会
  • Year and Date: 2013-10-05
• [Remarks] ゲノム生物学研究分野
  • URL: http://www.ncc.go.jp/jp/nccri/divisions/genome_biology/index.html