Development of cancer therapy for chromatin remodeling deficient cancer

• Project/Area Number: 26830122
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor therapeutics
• Research Institution: National Cancer Center Japan
• Principal Investigator: Ogiwara Hideaki 国立研究開発法人国立がん研究センター, 研究所, 研究員 (40568953)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: ARID1A / Epigenetics / Chromatin Remodeling / Synthetic Lethal / Molecular Target Therapy

Outline of Final Research Achievements

The SWI/SNF chromatin remodeling gene ARID1A is frequently aberrant in ovarian and other many common cancers without effective therapies. A druggable vulnerability of ARID1A-deficient cancers would be useful for treating such cancers. Here, we show that compound X preferentially decrease survival of ARID1A-deficient cells and induce apoptosis in ARID1A-deficient cells.

Research Products

• [Journal Article] Targeting p300 Addiction in CBP-Deficient Cancers Causes Synthetic Lethality by Apoptotic Cell Death due to Abrogation of MYC Expression. (2016)
  • Author(s): Ogiwara H, Sasaki M, Mitachi T, Oike T, Higuchi S, Tominaga Y, Kohno T.
  • Journal Title: Cancer Discov. Volume: 6 Pages: 430-445
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] SETDB1, HP1 and SUV39 promote repositioning of 53BP1 to extend resection during homologous recombination in G2 cells (2015)
  • Author(s): Meryem Alagoz, Yoko Katsuki, Hideaki Ogiwara, Tomoo Ogi, Atsushi Shibata, Andreas Kakarougkas, and Penny Jeggo
  • Journal Title: Nucleic Acids Research Volume: 43(16) Issue: 16 Pages: 7931-7944
  • DOI: 10.1093/nar/gkv722
  • NAID: 120006986903
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The EGFR mutation status affects the relative biological effectiveness of carbon-ion beams in non-small cell lung carcinoma cells. (2015)
  • Author(s): Amornwichet N, Oike T, Shibata A, Nirodi CS, Ogiwara H, Makino H, Kimura Y, Hirota Y, Isono M, Yoshida Y, Ohno T, Kohno T, Nakano T.
  • Journal Title: Sci Rep. Volume: 11 Issue: 1 Pages: 11305-11305
  • DOI: 10.1038/srep11305
  • Peer Reviewed / Open Access / Int'l Joint Research
• [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(4) Issue: 4 Pages: 617-30
  • DOI: 10.1016/j.molcel.2014.01.030
  • Peer Reviewed
• [Journal Article] Carbon-Ion Beam Irradiation Kills X-Ray-Resistant p53-Null Cancer Cells by Inducing Mitotic Catastrophe (2014)
  • Author(s): Amornwichet N, Oike T, Shibata A, Ogiwara H, Tsuchiya N, Yamauchi M, Saitoh Y, Sekine R, Isono M, Yoshida Y, Ohno T, Kohno T, Nakano T
  • Journal Title: PLoS One Volume: 9 Issue: 12 Pages: e115121-e115121
  • DOI: 10.1371/journal.pone.0115121
  • NAID: 120006986291
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Proposal for a synthetic lethality therapy using the paralog dependence of cancer cells-response (2014)
  • Author(s): Oike T, Ogiwara H, Nakano T, Kohno T
  • Journal Title: Cancer Res Volume: 74 Issue: 17 Pages: 4948-4949
  • DOI: 10.1158/0008-5472.can-14-0674
  • 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: 111 Issue: 2 Pages: 222-227
  • DOI: 10.1016/j.radonc.2014.03.015
  • Peer Reviewed / Acknowledgement Compliant
• [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 S, 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: 20 Issue: 12 Pages: 3087-3093
  • DOI: 10.1158/1078-0432.ccr-14-0107
  • Peer Reviewed / Acknowledgement Compliant
• [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-I, Ogiwara H, Nagase T, Kohno T, and Yasui A.
  • Journal Title: Cancer Res. Volume: 74 Issue: 9 Pages: 2465-2475
  • DOI: 10.1158/0008-5472.can-13-3608
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [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 Thoracic Oncol Volume: 9 Issue: 5 Pages: 622-630
  • DOI: 10.1097/jto.0000000000000135
  • Peer Reviewed / Acknowledgement Compliant
• [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: 55 Issue: 4 Pages: 613-628
  • DOI: 10.1093/jrr/rrt227
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Possible involvement of LKB1-AMPK signaling in non-homologous end joining. (2014)
  • Author(s): Ui A, Ogiwara H, Nakajima S, Kanno S-I, Watanabe R, Harata M, Okayama H, Harris CC, Yokota J, Yasui A and Kohno T
  • Journal Title: Oncogene Volume: 33 Issue: 13 Pages: 1640-1648
  • DOI: 10.1038/onc.2013.125
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] SNF5/SMARCB1変異がんにおける合成致死遺伝子の探索 (2015)
  • Author(s): 三田地隆史、板垣宏、河野隆志、荻原秀明
  • Organizer: BMB2015（第38回日本分子生物学会年会、第88回日本生化学会大会 合同大会）
  • Place of Presentation: 兵庫県 神戸ポートアイランド
  • Year and Date: 2015-12-01
• [Presentation] Development of Novel Cancer Therapeutics using Synthetic Lethality (2015)
  • Author(s): Takashi Kohno, Hideaki Ogiwara, Motonobu Saito
  • Organizer: 第53回日本癌治療学会学術集会
  • Place of Presentation: 京都府 国立京都国際会館
  • Year and Date: 2015-10-29
  • Invited
• [Presentation] CBP欠失がんにおけるp300依存性を標的とした合成致死治療法 (2015)
  • Author(s): 荻原秀明、佐々木麻里子、尾池貴洋、河野隆志
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 愛知県 名古屋国際会議場
  • Year and Date: 2015-10-08
• [Presentation] がん遺伝子融合とクロマチン制御異常を標的とした肺がん個別化治療 (2015)
  • Author(s): 河野隆志、荻原秀明、齋藤元伸
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 愛知県 名古屋国際会議場
  • Year and Date: 2015-10-08
  • Invited
• [Presentation] HER2/HER3シグナル阻害によるNRG1遺伝子融合陽性肺がんの治療 (2015)
  • Author(s): 中奥 敬史, 蔦 幸治、村山 貴彦、中田 飛鳥, 白石 航也、荻原 秀明 、金 永学 、三嶋 理晃、後藤 典子, 河野 隆志
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 愛知県 名古屋国際会議場
  • Year and Date: 2015-10-08
• [Presentation] Druggable oncogene fusions in invasive mucinous lung adenocarcinoma (2015)
  • Author(s): Takashi Nakaoku, Koji Tsuta, Hitoshi Ichikawa, Kouya Shiraishi, Hiromi Sakamoto, Masato Enari, Koh Furuta, Yoko Shimada, Hideaki Ogiwara, Shun-ichi Watanabe, Hiroshi Nokihara, Kazuki Yasuda, Masaki Hiramoto, Takao Nammo, Young Hak Kim, Michiaki Mishima, Jun Yokota, Teruhiko Yoshida, and Takashi Kohno
  • Organizer: AACR Annual Meeting 2015
  • Place of Presentation: Pennsylvania Convenetion Center Philadelphia, Pennsylvania, USA
  • Year and Date: 2015-04-18
  • Int'l Joint Research
• [Presentation] Synthetic lethality-based therapy targeting paralogous genes in cancer with chromatin regulating gene deficiencies (2014)
  • Author(s): Hideaki Ogiwara, Takahiro Oike, Takashi Kohno
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] Synthetic lethality-based treatment strategy for cancers deficient in chromatin remodeling factor BRG1 (2014)
  • Author(s): Takahiro Oike, Hideaki Ogiwara, Yuichi Tominaga, Kentaro Ito, Koji Tsuta, Tatsuji Mizukami, Yoko Shimada, Hisanori Isomura, Mayumi Komachi, Koh Furuta, Shun-ichi Watanabe, Takashi Nakano, JunYokota, Takashi Kohno
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2014-09-25 – 2014-09-27
• [Remarks] 遺伝子変異に基づく合成致死性を利用したがん治療法の開発（ゲノム生物学研究分野）
  • URL: http://www.nccri.ncc.go.jp/s010/010/020/20151209212406.html
• [Remarks] 国立がん研究センター研究所 分子診断・個別化医療開発グループ ゲノム生物学研究分野
  • URL: http://www.ncc.go.jp/jp/nccri/divisions/genome_biology/index.html