Investigation of a new drug based on DNA mutation analysis in ovarian cancer.

• Project/Area Number: 25462590
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Kyoto University
• Principal Investigator: Matsumura Noriomi 京都大学, 医学(系)研究科(研究院), 准教授 (20452336)
• Co-Investigator(Kenkyū-buntansha): Konishi Ikuo 京都大学医学研究科器官外科学, 婦人科学産科学, 名誉教授 (90192062) ; Mori Seiichi 公益財団法人がん研究会, 研究員 (10334814)
• 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: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 卵巣癌 / 遺伝子異常 / バイオマーカー / 卵巣がん / 遺伝子発現解析 / 分子標的療法 / 遺伝子

Outline of Final Research Achievements

We conducted a research about high-grade serous ovarian carcinoma (HGSOC), poor prognostic histopathological subtype of ovarian carcinoma. We established a novel histopathological classification that correlates with the four gene expression subtypes and taxane sensitivity of HGSOC. This result may identify a biomarker to select a taxane-containing chemotherapeutic regimen in HGSOC.

Research Products

• [Journal Article] Prediction of taxane and platinum sensitivity in ovarian cancer based on gene expression profiles. (2016)
  • Author(s): Murakami R, Matsumura N, Brown JB, Wang Z, Yamaguchi K, Abiko K, Yoshioka Y, Hamanishi J, Baba T, Koshiyama M, Mandai M, Yamada R, Konishi I.
  • Journal Title: Gynecol Oncol. Volume: 141 Issue: 1 Pages: 49-56
  • DOI: 10.1016/j.ygyno.2016.02.027
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] The BMP signaling pathway leads to enhanced proliferation in serous ovarian cancer-a potential therapeutic target. (2015)
  • Author(s): Peng J, Yoshioka Y, Mandai M, et al
  • Journal Title: Mol Carcinog Volume: Epub ahead of print Issue: 4 Pages: 1-11
  • DOI: 10.1002/mc.22283
  • Peer Reviewed / Open Access
• [Journal Article] Chemotherapy Induces Programmed Cell Death-Ligand 1 Overexpression via the Nuclear Factor-κB to Foster an Immunosuppressive Tumor Microenvironment in Ovarian Cancer. (2015)
  • Author(s): Peng J, Hamanishi J, Matsumura N, Abiko K, Murat K, Baba T, Yamaguchi K, Horikawa N, Hosoe Y, Murphy SK, Konishi I, Mandai M.
  • Journal Title: Cancer Res. Volume: 75 Issue: 23 Pages: 5034-5045
  • DOI: 10.1158/0008-5472.can-14-3098
  • Peer Reviewed
• [Journal Article] Ovarian clear cell carcinoma meets metabolism; HNF-1β confers survival benefits through the Warburg effect and ROS reduction. (2015)
  • Author(s): Mandai M, Amano Y, Yamaguchi K, Matsumura N, Baba T, Konishi I.
  • Journal Title: Oncotarget. Volume: 6 Issue: 31 Pages: 30704-30714
  • DOI: 10.18632/oncotarget.5228
  • NAID: 120005756271
  • Peer Reviewed
• [Journal Article] Safety and Anti-tumor Activity of Anti–PD-1 Antibody (Nivolumab: ONO-4538/BMS-936558) in Patients with Platinum-resistant Ovarian Cancer. (2015)
  • Author(s): Hamanishi, J., M. Mandai, T. Ikeda, M. Minami, A. Kawaguchi, T. Murayama, M. Kanai, Y. Mori, S. Matsumoto, S. Chikuma, N. Matsumura, K. Abiko, T. Baba, K. Yamaguchi, A. Ueda, Y. Hosoe, S. Morita, M. Yokode, A. Shimizu, T. Honjo, I. Konishi.
  • Journal Title: J Clin Oncol Volume: 33 Issue: 34 Pages: 4015-22
  • DOI: 10.1200/jco.2015.62.3397
  • Peer Reviewed / Open Access
• [Journal Article] Metabolic alterations caused by HNF1β expression in ovarian clear cell carcinoma contribute to cell survival. (2015)
  • Author(s): Amano Y, Mandai M, Yamaguchi K, Matsumura N, Kharma B, Baba T, Abiko K, Hamanishi J, Yoshioka Y, Konishi I.
  • Journal Title: Oncotarget. Volume: 6 Issue: 28 Pages: 26002-26017
  • DOI: 10.18632/oncotarget.4692
  • Peer Reviewed
• [Journal Article] Venous thromboembolism, interleukin-6 and survival outcomes in patients with advanced ovarian clear cell carcinoma. (2015)
  • Author(s): Matsuo K, Hasegawa K, Yoshino K, Murakami R, Hisamatsu T, Stone RL, Previs RA, Hansen JM, Ikeda Y, Miyara A, Hiramatsu K, Enomoto T, Fujiwara K, Matsumura N, Konishi I, Roman LD, Gabra H, Fotopoulou C, Sood AK
  • Journal Title: Eur J Cancer Volume: 51 Issue: 14 Pages: 1978-1988
  • DOI: 10.1016/j.ejca.2015.07.012
  • Peer Reviewed
• [Journal Article] IFN-γ from lymphocytes induces PD-L1 expression and promotes progression of ovarian cancer (2015)
  • Author(s): Abiko K, Matsumura N, Hamanishi J, Horikawa N, Murakami R, Yamaguchi K, Yoshioka Y, Baba T, Konishi I, Mandai M
  • Journal Title: British Journal of Cancer Volume: 未確定 Issue: 9 Pages: 1501-1509
  • DOI: 10.1038/bjc.2015.101
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Two cases of recurrent ovarian clear cell carcinoma treated with sorafenib. (2014)
  • Author(s): Koshiyama M, Matsumura N, Baba T, Yamaguchi K, Yoshioka Y, Konishi I.
  • Journal Title: Cancer Biol Ther. Volume: 15 Issue: 1 Pages: 22-5
  • DOI: 10.4161/cbt.26608
  • NAID: 120005367800
  • Peer Reviewed / Open Access
• [Journal Article] Humoral hypercalcemia caused by uterine corpus carcinosarcoma consisting of squamous cell carcinoma in its epithelial component. (2014)
  • Author(s): Takamatsu S, Matsumura N, Baba T, Mandai M, Mikami Y, Konishi I.
  • Journal Title: J Obstet Gynaecol Res. Volume: 40 Issue: 1 Pages: 263-7
  • DOI: 10.1111/jog.12136
  • Peer Reviewed
• [Journal Article] An EMT spectrum defines an anoikis-resistant and spheroidogenic intermediate mesenchymal state that is sensitive to e-cadherin restoration by a src-kinase inhibitor, saracatinib (AZD0530). (2013)
  • Author(s): Huang RY, Wong MK, Tan TZ, Kuay KT, Ng AH, Chung VY, Chu YS, Matsumura N, Lai HC, Lee YF, Sim WJ, Chai C, Pietschmann E, Mori S, Low JJ, Choolani M, Thiery JP
  • Journal Title: Cell Death Dis. Volume: 4 Issue: 11 Pages: e915-e915
  • DOI: 10.1038/cddis.2013.442
  • Peer Reviewed
• [Journal Article] Recurrence of a carcinoid tumor of the ovary 13 years after the primary surgery: A case report. (2013)
  • Author(s): Amano Y, Mandai M, Baba T, Hamanishi J, Yoshioka Y, Matsumura N, Konishi I.
  • Journal Title: Oncol Lett. Volume: 6 Issue: 5 Pages: 1241-1244
  • DOI: 10.3892/ol.2013.1530
  • Peer Reviewed
• [Journal Article] A novel diagnostic criterion for lymph node metastasis in cervical cancer using multi-detector computed tomography. (2013)
  • Author(s): Yamanoi K, Matsumura N, Kido A, Baba T, Hamanishi J, Yamaguchi K, Yoshioka Y, Abou Taleb H, Togashi K, Konishi I.
  • Journal Title: Gynecol Oncol. Volume: 131 Issue: 3 Pages: 707-7
  • DOI: 10.1016/j.ygyno.2013.10.014
  • NAID: 120005357243
  • Peer Reviewed
• [Journal Article] Functional genomics identifies five distinct molecular subtypes with clinical relevance and pathways for growth control in epithelial ovarian cancer. (2013)
  • Author(s): Tan TZ, Miow QH, Huang RY, Wong MK, Ye J, Lau JA, Wu MC, Bin Abdul Hadi LH, Soong R, Choolani M, Davidson B, Nesland JM, Wang LZ, Matsumura N, Mandai M, Konishi I, Goh BC, Chang JT, Thiery JP, Mori S.
  • Journal Title: EMBO Mol Med. Volume: 5 Issue: 7 Pages: 983-998
  • DOI: 10.1002/emmm.201201823
  • Peer Reviewed
• [Journal Article] Utilization of genomic signatures to identify high efficacy candidate drugs for chemo-refractory endometrial cancers. (2013)
  • Author(s): Kharma B, Baba T, Mandai M, Matsumura N, Murphy SK, Kang HS, Yamanoi K, Hamanishi J, Yamaguchi K, Yoshioka Y, Konishi I.
  • Journal Title: Int J Cancer. Volume: 133 Issue: 9 Pages: 2234-44
  • DOI: 10.1002/ijc.28220
  • Peer Reviewed
• [Presentation] Integrated analysis of single nucleotide variants and copy number variants in ovarian clear cell adenocarcinoma (2015)
  • Author(s): Noriomi Matsumura、Ryuusuke Murkami、Koichiro Higasa、Takanobu Tsutsumi、J. B. Brown、Junzo Hamanishi、Ken Yamaguchi、Kaoru Abiko、Tsukasa Baba、Masafumi Koshiyama、Ryo Yamada、Fumihiko Matsuda、Yasushi Okuno、Ikuo Konishi
  • Organizer: 第53回日本癌治療学会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2015-10-29
  • Invited
• [Presentation] 卵巣癌の微小免疫環境解析と抗PD-1抗体療法の展望 (2015)
  • Author(s): 濱西 潤三、万代 昌紀、松村 謙臣、安彦 郁、村上 隆介、馬場 長、山口 建、小西 郁生
  • Organizer: 第53回日本癌治療学会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2015-10-29
  • Invited
• [Presentation] Identification through functional genomics screening of factors whose downregulation enhances the side population in ovarian cancer. (2015)
  • Author(s): Noriomi Matsumura, Koji Yamanoi, Susan K Murphy, Junzo Hamanishi, Kaoru Abiko, Ken Yamaguchi, Tsukasa Baba, Masafumi Koshiyama, Ikuo Konishi
  • Organizer: An AACR Special Conference on Advances in Ovarian Cancer Research
  • Place of Presentation: Hyatt Regency Orland
  • Year and Date: 2015-10-17
  • Int'l Joint Research
• [Presentation] Chemoimmunotherapy with PD-1 blockade and paclitaxel induce a potent antitumor immunity in ovarian cancers. (2015)
  • Author(s): Junzo Hamanishi, Jin Peng, Noriomi Matsumura, Kaoru Abiko, Tsukasa Baba, Ken Yamaguchi, Ikuo Konishi, Masaki Mandai
  • Organizer: An AACR Special Conference on Advances in Ovarian Cancer Research
  • Place of Presentation: Hyatt Regency Orland
  • Year and Date: 2015-10-17
• [Presentation] Inhibition of Snail-induced EMT promotes anti-tumor immune response in ovarian cancer. (2015)
  • Author(s): Mana Taki, Kaoru Abiko, Noriomi Matsumura, Tsukasa Baba, Junzo Hamanishi, Naoki Horikawa, Ikuo Konishi
  • Organizer: An AACR Special Conference on Advances in Ovarian Cancer Research
  • Place of Presentation: Hyatt Regency Orland
  • Year and Date: 2015-10-17
• [Presentation] Expression of VEGF in ovarian cancer suppresses tumor immunity through recruitment of myeloid derived suppressor cells. (2015)
  • Author(s): Naoki Horikawa, Kaoru Abiko, Noriomi Matsumura, Junzo Hamanishi, Susan K Murphy, Tsukasa Baba, Ken Yamaguchi, Masafumi Koshiyama, Ikuo Konishi
  • Organizer: An AACR Special Conference on Advances in Ovarian Cancer Research
  • Place of Presentation: Hyatt Regency Orland
  • Year and Date: 2015-10-17
• [Presentation] 卵巣癌細胞におけるanoikis抵抗遺伝子の同定：ABHD2発現低下は、シスプラチン抵抗性、side population増加ももたらし、予後不良と相関する (2014)
  • Author(s): 山ノ井康二、松村謙臣、安彦郁、山口建、吉岡弓子、濱西潤三、馬場長、越山雅文、小西郁生
  • Organizer: 第66回日本産科婦人科学会学術集会
  • Place of Presentation: 東京国際フォーラム
• [Presentation] 卵巣高異型度漿液性腺癌のmolecular subtypeを反映する新しい病理組織学的分類 (2014)
  • Author(s): 村上隆介、松村謙臣、吉原弘祐、濱西潤三、安彦郁、山口建、馬場長、吉岡弓子、小西郁生、榎本隆之
  • Organizer: 第66回日本産科婦人科学会学術集会
  • Place of Presentation: 東京国際フォーラム
• [Presentation] Role of SWI/SNF complex in Clear Cell Carcinoma of the ovary (CCC) (2014)
  • Author(s): Ken Yamaguchi, Hisham Abou-Taleb, Noriomi Matsumura, Yasuaki Amano, Koji Yamanoi, Ryusuke Murakami, Tsukasa Baba, Yumiko Yoshioka, Junzo Hamanishi, Masaki Mandai, Ikuo Konishi
  • Organizer: 第66回日本産科婦人科学会学術集会
  • Place of Presentation: 東京国際フォーラム
• [Presentation] Chemotherapy induces PD-L1 overexpression via NF-kB signal pathway in ovarian cancer (2014)
  • Author(s): Jin Peng, Junzo Hamanishi, Noriomi Matsumura, Kaoru Abiko, Tsukasa Baba, Ken Yamaguchi, Ikuo Konishi, Masaki Mandai
  • Organizer: 第66回日本産科婦人科学会学術集会
  • Place of Presentation: 東京国際フォーラム
• [Presentation] 卵巣癌腹膜播種のPD-L1発現は、間質内のリンパ球が分泌するIFN-γにより誘導される (2014)
  • Author(s): 安彦郁、松村謙臣、濱西潤三、堀川直城、Jin Peng、村上隆介、山口建、馬場長、小西郁生、万代昌紀
  • Organizer: 第66回日本産科婦人科学会学術集会
  • Place of Presentation: 東京国際フォーラム