分子標的治療耐性化メカニズムの網羅的探索

• Project/Area Number: 21H02795
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: National Cancer Center Japan
• Principal Investigator: 高阪 真路 国立研究開発法人国立がん研究センター, 研究所, 分野長 (00627119)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Project Status: Completed (Fiscal Year 2023)
• Budget Amount: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000); Fiscal Year 2023: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2022: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2021: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
• Keywords: ゲノム医学 / 薬剤耐性 / がん遺伝子 / ハイスループット機能解析

Outline of Research at the Start

保険医療によるがん遺伝子パネル検査が普及しつつあるが, 機能不明のバリアントの生物学的・臨床的意味づけを行うことが, 個別化医療の実現に向けた大きな課題となっている. 我々はハイスループットがん遺伝子機能解析法 (mixed-all-nominated-mutants-in-one method: MANO法)を開発した. 本研究開発においてはがん遺伝子の網羅的機能解析, MANO法を用いた分子標的薬耐性化メカニズムの解明, 併用療法による耐性化解除の検討, リキッドバイオプシーを用いた薬剤耐性化メカニズムの解明をマイルストーンとし, 薬剤耐性を克服する新たな治療法の開発を目指す.

Outline of Annual Research Achievements

がん遺伝子の網羅的機能解析として、68遺伝子、243バリアントについて、マウス線維芽細胞株にがん遺伝子を導入し、focus formation assay及びMANO法によるがん化能評価を行った。 さらに、様々ながん細胞株にがん遺伝子を導入し、表現型の変化をfocus formation assayおよびsoft agar colony formation assayで評価した。 MANO法を用いた分子標的薬耐性化メカニズムの解明として、様々ながん細胞株にがん遺伝子243バリアントを導入して、各分子標的薬に対する薬剤感受性をMANO法を用いて評価したところ、分子標的薬に対する耐性マーカーが複数同定された。また、取得された薬剤耐性バリアントを個別に細胞株に導入し、耐性化を検証した。さらに薬剤投与下でmRNAの発現解析、タンパク質リン酸化の解析を行い、耐性化のメカニズムを評価した。併用療法による耐性化解除の検討として、複数のバリアントの組み合わせを遺伝子導入した細胞株を用意し、薬剤併用試験のアッセイ系を確立した。さらに、MAP2K1の複数のがん遺伝子の組み合わせによりがん化した発がんモデルを用いて、薬剤併用試験による最適化薬剤の組み合わせおよび最適濃度の評価し、論文発表を行った (Mizuno S, et al. Mol Cancer Ther., 2023)。リキッドバイオプシーを用いた薬剤耐性化メカニズムの解明として、末梢血及び病変部組織 (生検・手術検体または過去に保存された FFPE ブロック等)より, DNA/RNA を抽出し, 血漿中に存在する cfDNA/RNAを精製し, ターゲットシークエンス, トランスクリプトーム解析を行い, 耐性・奏効性と関連するバイオマーカーの同定を行った (Koyama T, et al. Cancer Discov., 2023)。

Research Progress Status

令和5年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

令和5年度が最終年度であるため、記入しない。

Research Products

• [Journal Article] Analysis of quality metrics in comprehensive cancer genomic profiling using a dual DNA-RNA panel (2024)
  • Author(s): Watanabe K, Kohsaka S, Tatsuno K, Shinozaki-Ushiku A, Isago H, Kage H, Ushiku T, Aburatani H, Mano H, Oda K
  • Journal Title: Pract Lab Med Volume: 39 Pages: 368-368
  • DOI: 10.1016/j.plabm.2024.e00368
  • Peer Reviewed / Open Access
• [Journal Article] The development of a custom RNA-sequencing panel for the identification of predictive and diagnostic biomarkers in glioma (2024)
  • Author(s): Shirai Y, Ueno T, Kojima S, Ikeuchi H, Kitada R, Koyama T, Takahashi F, Takahashi K, Ichimura K, Yoshida A, Sugino H, Mano H, Narita Y, Takahashi M, Kohsaka S
  • Journal Title: Journal of Neuro-Oncology Volume: 167 Issue: 1 Pages: 75-88
  • DOI: 10.1007/s11060-024-04563-z
  • Peer Reviewed / Open Access
• [Journal Article] A Learning Program for Treatment Recommendations by Molecular Tumor Boards and Artificial Intelligence (2024)
  • Author(s): Sunami Kuniko、Naito Yoichi、Koyama Takafumi et.al
  • Journal Title: JAMA Oncology Volume: 10 Issue: 1 Pages: 95-95
  • DOI: 10.1001/jamaoncol.2023.5120
  • Peer Reviewed / Open Access
• [Journal Article] Inflammatory Rhabdomyoblastic Tumor: Clinicopathologic and Molecular Analysis of 13 Cases (2024)
  • Author(s): Odate T, Satomi K, Kubo T, Matsushita Y, Ueno T, Kurose A, Shomori K, Nakai T, Watanabe R, Segawa K, Ohshika S, Miyake N, Kudo S, Shimoi T, Kobayashi E, Komiyama M, Yoshimoto S, Nakatani F, Kawai, A, Yatabe Y, Kohsaka S, Ichimura K, Ichikawa H, Yoshida Akihiko
  • Journal Title: Modern Pathology Volume: 37 Issue: 1 Pages: 100359-100359
  • DOI: 10.1016/j.modpat.2023.100359
  • Peer Reviewed / Open Access
• [Journal Article] Multiomic molecular characterization of the response to combination immunotherapy in MSS/pMMR metastatic colorectal cancer (2024)
  • Author(s): Takei S、Tanaka Y、Lin Yi-Tzu、Koyama S、Fukuoka S、Hara H、Nakamura Y、Kuboki Y、Kotani D、Kojima T、Bando H、Mishima S、Ueno T、Kojima S、Wakabayashi M、Sakamoto N、Kojima M、Kuwata T、Yoshino T、Nishikawa H、Mano H、Endo I、Shitara K、Kawazoe A
  • Journal Title: Journal for ImmunoTherapy of Cancer Volume: 12 Issue: 2 Pages: 8210-8210
  • DOI: 10.1136/jitc-2023-008210
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Case report and literature review: exploration of molecular therapeutic targets in recurrent malignant meningioma through comprehensive genetic analysis with Todai OncoPanel (2023)
  • Author(s): Ohara K, Miyawaki S, Nakatomi H, Okano A, Teranishi Y, Shinya Y, Ishigami D, Hongo H, Takayanagi S, Tanaka S, Shinozaki-Ushiku A, Kohsaka S, Kage H, Oda K, Miyagawa K, Aburatani H, Mano H, Tatsuno K, Saito N
  • Journal Title: Front Neurol Volume: 14 Pages: 1270046-1270046
  • DOI: 10.3389/fneur.2023.1270046
  • Peer Reviewed / Open Access
• [Journal Article] Promoter swapping of truncated PDGFRB drives Ph-like acute lymphoblastic leukemia (2023)
  • Author(s): Miyazaki Bunpei、Ueno Toshihide、Sugiyama Masanaka、Kojima Shinya、Arakawa Ayumu、Tao Kayoko、Tanimura Kazuki、Shiraishi Kouya、Yagishita Shigehiro、Kohsaka Shinji、Kato Mamoru、Kiyokawa Nobutaka、Goto Yasushi、Yatabe Yasushi、Hamada Akinobu、Mano Hiroyuki、Ogawa Chitose、Tanaka Yosuke
  • Journal Title: npj Precision Oncology Volume: 7 Issue: 1 Pages: 132-132
  • DOI: 10.1038/s41698-023-00485-7
  • Peer Reviewed / Open Access
• [Journal Article] Detection of Novel Tyrosine Kinase Fusion Genes as Potential Therapeutic Targets in Bone and Soft Tissue Sarcomas Using DNA/RNA-based Clinical Sequencing (2023)
  • Author(s): Hasegawa Nobuhiko、Hayashi Takuo、Niizuma Hidetaka、Kikuta Kazutaka、Imanishi Jungo、Endo Makoto、Ikeuchi Hiroshi、Sasa Keita、Sano Kei、Hirabayashi Kaoru、Takagi Tatsuya、Ishijima Muneaki、Kato Shunsuke、Kohsaka Shinji、Saito Tsuyoshi、Suehara Yoshiyuki
  • Journal Title: Clinical Orthopaedics & Related Research Volume: 482 Issue: 3 Pages: 549-563
  • DOI: 10.1097/corr.0000000000002901
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Subclonal accumulation of immune escape mechanisms in microsatellite instability-high colorectal cancers (2023)
  • Author(s): Kobayashi Y, Niida A, Nagayama S, Saeki K, （中略）, Mizuno S, Kawazu M, Kohsaka S, Ueno T, Mano H, Ishihara S, Uemura M, Mori M, Doki Y, Eguchi H, Oshima M, Suzuki Y, Shibata T, Mimori K.
  • Journal Title: Br J Cancer Volume: 129 Issue: 7 Pages: 1105-1118
  • DOI: 10.1038/s41416-023-02395-8
  • Peer Reviewed / Open Access
• [Journal Article] Extensive analysis of 59 sarcoma‐related fusion genes identified pazopanib as a potential inhibitor to <scp><i>COL1A1‐PDGFB</i></scp> fusion gene (2023)
  • Author(s): Hirose Takeshi、Ikegami Masachika、Kojima Shinya、Yoshida Akihiko、Endo Makoto、Shimada Eijiro、Kanahori Masaya、Oyama Ryunosuke、Matsumoto Yoshihiro、Nakashima Yasuharu、Kawai Akira、Mano Hiroyuki、Kohsaka Shinji
  • Journal Title: Cancer Science Volume: 114 Issue: 10 Pages: 4089-4100
  • DOI: 10.1111/cas.15915
  • Peer Reviewed / Open Access
• [Journal Article] Clinical Activity and Exploratory Resistance Mechanism of Milademetan, an MDM2 Inhibitor, in Intimal Sarcoma with <i>MDM2</i> Amplification: An Open-Label Phase Ib/II Study (2023)
  • Author(s): Koyama Takafumi、Shimizu Toshio、Kojima Yuki、Sudo Kazuki、Okuma Hitomi Sumiyoshi、Shimoi Tatsunori、Ichikawa Hitoshi、Kohsaka Shinji、Sadachi Ryo、Hirakawa Akihiro、Yoshida Akihiko、Ando Reiko Makihara、Ueno Toshihide、Yanagaki Mitsuru、Matsui Naoko、Nakamura Kenichi、Yamamoto Noboru、Yonemori Kan
  • Journal Title: Cancer Discovery Volume: 13 Issue: 8 Pages: 1814-1825
  • DOI: 10.1158/2159-8290.cd-23-0419
  • Peer Reviewed / Open Access
• [Journal Article] The pathogenic role of the BRCA2 c.7847C>T (p.Ser2616Phe) variant in breast and ovarian cancer predisposition (2023)
  • Author(s): Yamazawa Kazuki、Sugano Kokichi、Tanakaya Kohji、Inoue Satomi、Murakami Haruka、Nakashima Moeko、Adachi Masataka、Oki Shinya、Makabe Takeshi、Yamashita Hiroshi、Ueki Arisa、Sasaoka Ayako、Nakashoji Ayako、Kinoshita Takayuki、Matsunaga Tatsuo、Arai Masami、Nakamura Seigo、Miyata Hiroaki、Ikegami Masachika, et al.
  • Journal Title: Cancer Science Volume: - Issue: 7 Pages: 2993-3002
  • DOI: 10.1111/cas.15799
  • Peer Reviewed / Open Access
• [Journal Article] Molecular pathology quality control in Southeast Asia: Results of a multiregional quality assurance study from MASTER KEY Asia (2023)
  • Author(s): Okuma Hitomi Sumiyoshi、Yoshida Hiroshi、Kobayashi Yoshihisa、Arakaki Motoko、Mizoguchi Chiharu、Inagaki Lina、Voon Pei Jye、Malik Bin Ismail Adam、Fen Soo Hoo Hwoei、Yusak Suhana、Severino B. Imasa Marcelo、Nguyen Huy Thinh、Thai Anh Tu、Kohsaka Shinji、Mano Hiroyuki、Yonemori Kan、Nakamura Kenichi、Yatabe Yasushi
  • Journal Title: Cancer Science Volume: in press Issue: 6 Pages: 2664-2673
  • DOI: 10.1111/cas.15790
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Clinical utility of Todai OncoPanel in the setting of approved comprehensive cancer genomic profiling tests in Japan (2023)
  • Author(s): Kage Hidenori、Shinozaki‐Ushiku Aya、Tanikawa Michihiro、Aburatani Hiroyuki、Mano Hiroyuki、Miyagawa Kiyoshi、Oda Katsutoshi
  • Journal Title: Cancer Science Volume: 114 Issue: 4 Pages: 1710-1717
  • DOI: 10.1111/cas.15717
  • Peer Reviewed / Open Access
• [Journal Article] Expression of paired box 9 defines an aggressive subset of lung adenocarcinoma preferentially occurring in smokers (2023)
  • Author(s): Hayashi Takuo、Kishi Monami、Takamochi Kazuya、Hosoya Masaki、Kohsaka Shinji、Kishikawa Satsuki、Ura Ayako、Sano Kei、Sasahara Noriko、Suehara Yoshiyuki、Takahashi Fumiyuki、Saito Tsuyoshi、Suzuki Kenji、Yao Takashi、the Tokyo Metropolitan Innovative Oncology Research Group (TMIG)
  • Journal Title: Histopathology Volume: 82 Issue: 5 Pages: 672-683
  • DOI: 10.1111/his.14853
  • Peer Reviewed / Open Access
• [Journal Article] Genome Doubling Shapes High-Grade Transformation and Novel EWSR1::LARP4 Fusion Shows SOX10 Immunostaining in Hyalinizing Clear Cell Carcinoma of Salivary Gland (2023)
  • Author(s): Kobayashi Kenya、Kawazu Masahito、Yoshimoto Seiichi、Ueno Toshihide、Omura Go、Saito Yuki、Ando Mizuo、Ryo Eigitsu、Sakyo Airi、Yoshida Akihiko、Yatabe Yasushi、Mano Hiroyuki、Mori Taisuke
  • Journal Title: Laboratory Investigation Volume: 103 Issue: 10 Pages: 100213-100213
  • DOI: 10.1016/j.labinv.2023.100213
  • Peer Reviewed
• [Journal Article] Strategic Approach to Heterogeneity Analysis of Cutaneous Adnexal Carcinomas Using Computational Pathology and Genomics (2023)
  • Author(s): Nishimura Yuuki、Ryo Eijitsu、Inoue Satoshi、Kawazu Masahito、Ueno Toshihide、Namikawa Kenjiro、Takahashi Akira、Ogata Dai、Yoshida Akihiko、Yamazaki Naoya、Mano Hiroyuki、Yatabe Yasushi、Mori Taisuke
  • Journal Title: JID Innovations Volume: 3 Issue: 6 Pages: 100229-100229
  • DOI: 10.1016/j.xjidi.2023.100229
  • Peer Reviewed / Open Access
• [Journal Article] Dramatic response to entrectinib in a patient with malignant peripheral nerve sheath tumor harboring novel SNRNP70-NTRK3 fusion gene (2023)
  • Author(s): Kobayashi H, Makise N, Shinozaki-Ushiku A, Zhang L, Ishibashi Y, Ikegami M, Tsuda Y, Kohsaka S, Ushiku T, Oda K, Miyagawa K, Aburatani H, Mano H, Tanaka S.
  • Journal Title: Genes Chromosomes Cancer. Volume: 62 Issue: 1 Pages: 47-51
  • DOI: 10.1002/gcc.23089
  • Peer Reviewed
• [Journal Article] Concordance Between Recommendations From Multidisciplinary Molecular Tumor Boards and Central Consensus for Cancer Treatment in Japan. (2022)
  • Author(s): Naito Y, Sunami K, Kage H, Komine K, Amano T, Imai M, Koyama T, Ennishi D, Kanai M, Kenmotsu H, Maeda T, Morita S, Sakai D, Watanabe K, Shirota H, Kinoshita I, Yoshioka M, Mamesaya N, Ito M, Kohsaka S, Saigusa Y, Yamamoto K, Hirata M, Tsuchihara K, Yoshino T.
  • Journal Title: JAMA Netw Open. Volume: 5 Issue: 12 Pages: 2245081-2245081
  • DOI: 10.1001/jamanetworkopen.2022.45081
  • Peer Reviewed / Open Access
• [Journal Article] High-Throughput Functional Evaluation of MAP2K1 Variants in Cancer (2022)
  • Author(s): Mizuno Sho、Ikegami Masachika、Koyama Takafumi、Sunami Kuniko、Ogata Dai、Kage Hidenori、Yanagaki Mitsuru、Ikeuchi Hiroshi、Ueno Toshihide、Tanikawa Michihiro、Oda Katsutoshi、Osuga Yutaka、Mano Hiroyuki、Kohsaka Shinji
  • Journal Title: Molecular Cancer Therapeutics Volume: 22 Issue: 2 Pages: 227-239
  • DOI: 10.1158/1535-7163.mct-22-0302
  • Peer Reviewed / Open Access
• [Journal Article] Identification of novel prognostic and predictive biomarkers in salivary duct carcinoma via comprehensive molecular profiling (2022)
  • Author(s): Kohsaka S, Tada Y, Okami K, et al.
  • Journal Title: NPJ Precis Oncol. Volume: 6 Issue: 1 Pages: 82-82
  • DOI: 10.1038/s41698-022-00324-1
  • Peer Reviewed / Open Access
• [Journal Article] C-CAT: The National Datacenter for Cancer Genomic Medicine in Japan (2022)
  • Author(s): Kohno T, Kato M, Kohsaka S, Sudo T, Tamai I, Shiraishi Y, Okuma Y, Ogasawara D, Suzuki T, Yoshida T, Mano H
  • Journal Title: Cancer Discov Volume: 12 Issue: 11 Pages: 2509-2515
  • DOI: 10.1158/2159-8290.cd-22-0417
  • Peer Reviewed / Open Access
• [Journal Article] Primary Intracranial Spindle Cell Sarcoma, DICER1-Mutant with MDM2 Amplification Diagnosed on the Basis of Extensive Molecular Profiling (2022)
  • Author(s): Nejo Takahide、Takayanagi Shunsaku、Tanaka Shota、Shinozaki-Ushiku Aya、Kohsaka Shinji、Nagata Keisuke、Yokoyama Munehiro、Sora Shigeo、Ushiku Tetsuo、Mukasa Akitake、Aburatani Hiroyuki、Mano Hiroyuki、Saito Nobuhito
  • Journal Title: Clinical Medicine Insights: Case Reports Volume: 15 Pages: 117954762211311-117954762211311
  • DOI: 10.1177/11795476221131189
  • Peer Reviewed / Open Access
• [Journal Article] Novel Calcium-Binding Ablating Mutations Induce Constitutive RET Activity and Drive Tumorigenesis (2022)
  • Author(s): Tabata Junya、Nakaoku Takashi、Araki Mitsugu、Yoshino Ryunosuke、Kohsaka Shinji、Otsuka Ayaka、Ikegami Masachika、Ui Ayako、Kanno Shin-ichiro、Miyoshi Keiko、Matsumoto Shigeyuki、Sagae Yukari、Yasui Akira、Sekijima Masakazu、Mano Hiroyuki、Okuno Yasushi、Okamoto Aikou、Kohno Takashi
  • Journal Title: Cancer Research Volume: 82 Issue: 20 Pages: 3751-3762
  • DOI: 10.1158/0008-5472.can-22-0834
  • Peer Reviewed / Open Access
• [Journal Article] Survival benefit of HER2-targeted or androgen deprivation therapy in salivary duct carcinoma (2022)
  • Author(s): Kawakita Daisuke、Nagao Toshitaka、Takahashi Hideaki、Kano Satoshi、Honma Yoshitaka、Hirai Hideaki、Saigusa Natsuki、Akazawa Kohei、Tani Kaori、Ojiri Hiroya、Tsukahara Kiyoaki、Ozawa Hiroyuki、Okami Kenji、Kondo Takahito、Togashi Takafumi、Fushimi Chihiro、Shimura Tomotaka、Matsuki Takashi、Tada Yuichiro
  • Journal Title: Therapeutic Advances in Medical Oncology Volume: 14 Pages: 175883592211195-175883592211195
  • DOI: 10.1177/17588359221119538
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Chronological improvement in precision oncology implementation in Japan (2022)
  • Author(s): Sunami K, Naito Y, Komine K, Amano T, Ennishi D, Imai M, Kage H, Kanai M, Kenmotsu H, Koyama T, Maeda T, Morita S, Sakai D, Kohsaka S, Tsuchihara K, Saigusa Y, Yoshino T
  • Journal Title: Cancer Sci Volume: 113 Issue: 11 Pages: 3995-4000
  • DOI: 10.1111/cas.15517
  • Peer Reviewed / Open Access
• [Journal Article] A multicenter investigator-initiated Phase 2 trial of E7090 in patients with advanced or recurrent solid tumor with fibroblast growth factor receptor (FGFR) gene alteration: FORTUNE trial (2022)
  • Author(s): Chiba Y, Sudo K, Kojima Y, Okuma H, Kohsaka S, Machida R, Ichimura M, Anjo K, Kurishita K, Okita N, Nakamura K, Kinoshita I, Takahashi M, Matsubara J, Kusaba H, Yonemori K, Takahashi M
  • Journal Title: BMC Cancer Volume: 22 Issue: 1 Pages: 869-869
  • DOI: 10.1186/s12885-022-09949-8
  • Peer Reviewed / Open Access
• [Journal Article] Recommendations related to the analytical equivalence assessment of gene panel testing (2022)
  • Author(s): Nagai Sumimasa、Nishihara Hiroshi、Suzuki Takayoshi、Nishio Kazuto、Taniguchi Hiroya、Tsuchihara Katsuya、Nakamura Kohei、Takamatsu Reika、Ueno Toshihide、Aburatani Hiroyuki、Kohno Takashi、Kohsaka Shinji
  • Journal Title: Cancer Science Volume: 113 Issue: 10 Pages: 3282-3290
  • DOI: 10.1111/cas.15513
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Expert panel consensus recommendations on the use of circulating tumor DNA assays for patients with advanced solid tumors (2022)
  • Author(s): Imai M, Nakamura Y, Sunami K, Kage H, Komine K, Koyama T, Amano T, Ennishi D, Kanai M, Kenmotsu H, Maeda T, Morita S, Sakai D, Bando H, Makiyama A, Suzuki T, Hirata M, Kohsaka S, Tsuchihara K, Naito Y, Yoshino T
  • Journal Title: Cancer Sci Volume: 113 Issue: 11 Pages: 3646-3656
  • DOI: 10.1111/cas.15504
  • Peer Reviewed / Open Access
• [Journal Article] Feasibility and clinical utility of comprehensive genomic profiling of hematological malignancies (2022)
  • Author(s): Fukuhara S, Oshikawa-Kumade Y, Kohsaka S et al.
  • Journal Title: Cancer Sci Volume: 113 Issue: 8 Pages: 2763-2777
  • DOI: 10.1111/cas.15427
  • Peer Reviewed / Open Access
• [Journal Article] Clinical relevance of PD-L2 expression in surgically resected lung adenocarcinoma. (2022)
  • Author(s): Takamochi K, Hara K, Hayashi T, Kohsaka S, Takahashi F, Suehara Y, Shimokawa M, Suzuki K.
  • Journal Title: Lung Cancer Volume: 168 Pages: 50-58
  • DOI: 10.1016/j.lungcan.2022.04.011
  • Peer Reviewed / Open Access
• [Journal Article] Tumor mutational burden measurement using comprehensive genomic profiling assay (2022)
  • Author(s): Kage Hidenori、Kohsaka Shinji、Tatsuno Kenji、Ueno Toshihide、Ikegami Masachika、Zokumasu Koichi、Shinozaki-Ushiku Aya、Nagai Sumimasa、Aburatani Hiroyuki、Mano Hiroyuki、Oda Katsutoshi
  • Journal Title: Japanese Journal of Clinical Oncology Volume: 52 Issue: 8 Pages: 925-929
  • DOI: 10.1093/jjco/hyac063
  • Peer Reviewed
• [Journal Article] Genetic diagnosis of pseudomyxoma peritonei originating from mucinous borderline tumor inside an ovarian teratoma (2022)
  • Author(s): Taguchi Ayumi、Rokutan Hirofumi、Oda Katsutoshi、Tanikawa Michihiro、Tanimoto Saki、Sone Kenbun、Mori Mayuyo、Tsuruga Tetsushi、Kohsaka Shinji、Tatsuno Kenji、Shinozaki-Ushiku Aya、Miyagawa Kiyoshi、Mano Hiroyuki、Aburatani Hiroyuki、Ushiku Tetsuo、Osuga Yutaka
  • Journal Title: BMC Medical Genomics Volume: 15 Issue: 1 Pages: 51-51
  • DOI: 10.1186/s12920-022-01188-x
  • Peer Reviewed / Open Access
• [Journal Article] Composite Clonal Analysis Reveals Transition of NSCLC Subtypes Through Accumulation of Gene Mutations: A Case Report (2022)
  • Author(s): Ando T, Kage H, Shinozaki-Ushiku A, Tatsuno K, Tsutsumi S, Nagayama K, Nakajima J, Kohsaka S, Miyagawa K, Aburatani H, Mano H, Nagase T.
  • Journal Title: JTO Clin Res Rep Volume: 3 Issue: 2 Pages: 100277-100277
  • DOI: 10.1016/j.jtocrr.2022.100277
  • Peer Reviewed / Open Access
• [Journal Article] The Role of the EZH2 and H3K27me3 Expression as a Predictor of Clinical Outcomes in Salivary Duct Carcinoma Patients: A Large-Series Study With Emphasis on the Relevance to the Combined Androgen Blockade and HER2-Targeted Therapy (2022)
  • Author(s): Saigusa N, Hirai H, Kohsaka S, et al.
  • Journal Title: Front Oncol Volume: 11 Pages: 779882-779882
  • DOI: 10.3389/fonc.2021.779882
  • Peer Reviewed / Open Access
• [Journal Article] CIC-Mediated Modulation of MAPK Signaling Opposes Receptor Tyrosine Kinase Inhibitor Response in Kinase-Addicted Sarcoma (2022)
  • Author(s): Odintsov I, Ortiz MV, Khodos I, Mattar MS, Lui AJW, Kohsaka S, de Stanchina E, Bender JLG, Ladanyi M, Somwar R.
  • Journal Title: Cancer Res Volume: 82 Issue: 6 Pages: 1110-1127
  • DOI: 10.1158/0008-5472.can-21-1397
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Distinct properties of pure- and mixed-type high-grade fetal lung adenocarcinomas by genetic profiling and transcription factor expression. (2022)
  • Author(s): Kishikawa S, Hayashi T, Saito T, Takamochi K, Sasa K, Suehara Y, Takahashi F, Sasahara N, Kohsaka S, Suzuki K, Yao T
  • Journal Title: Virchows Arch Volume: 480 Issue: 3 Pages: 609-619
  • DOI: 10.1007/s00428-021-03247-7
  • Peer Reviewed
• [Journal Article] Preclinical assessment of combination therapy of EGFR tyrosine kinase inhibitors in a highly heterogeneous tumor model (2022)
  • Author(s): Ikeuchi H, Hirose T, Ikegami M, Takamochi K, Suzuki K, Mano H, Kohsaka S.
  • Journal Title: Oncogene Volume: 41 Issue: 17 Pages: 2470-2479
  • DOI: 10.1038/s41388-022-02263-4
  • Peer Reviewed / Open Access
• [Journal Article] MicroSEC; Sequence error filtering pipeline for formalin-fixed and paraffin-embedded samples. (2021)
  • Author(s): Ikegami M, Kohsaka S, Hirose T, Ueno T, Inoue S, Konomata N, Yamauchi H, Mori T, Sekine S, Inamoto Y, Yatabe Y, Kobayashi H, Tanaka S, Mano H.
  • Journal Title: Commun Biol Volume: 4 Issue: 1 Pages: 1396-1396
  • DOI: 10.1038/s42003-021-02930-4
  • Peer Reviewed / Open Access
• [Journal Article] Comparative Study on the Efficacy and Exposure of Molecular Target Agents in Non?small Cell Lung Cancer PDX Models with Driver Genetic Alterations (2021)
  • Author(s): Jo Hitomi、Yagishita Shigehiro、Hayashi Yoshiharu、Ryu Shoraku、Suzuki Mikiko、Kohsaka Shinji、Ueno Toshihide、Matsumoto Yuji、Horinouchi Hidehito、Ohe Yuichiro、Watanabe Shun-ichi、Motoi Noriko、Yatabe Yasushi、Mano Hiroyuki、Takahashi Kazuhisa、Hamada Akinobu
  • Journal Title: Molecular Cancer Therapeutics Volume: 21 Issue: 2 Pages: 359-370
  • DOI: 10.1158/1535-7163.mct-21-0371
  • Peer Reviewed / Open Access
• [Journal Article] Scapular Angiomatoid Fibrous Histiocytoma with EWSR1-CREB1 Fusion in an Adult Patient (2021)
  • Author(s): Kobayashi H, Makise N, Shinozaki-Ushiku A, Ishibashi Y, Ikegami M, Kohsaka S, Ushiku T, Oda K, Miyagawa K, Aburatani H, Mano H, Tanaka S.
  • Journal Title: Case Rep Orthop Volume: 2021 Pages: 9434222-9434222
  • DOI: 10.1155/2021/9434222
  • Peer Reviewed / Open Access
• [Journal Article] Programmed death-ligand 1 expression and its associations with clinicopathological features, prognosis, and driver oncogene alterations in surgically resected lung adenocarcinoma (2021)
  • Author(s): Takamochi K, Hara K, Hayashi T, Kohsaka S, Takahashi F, Suehara Y, Suzuki K.
  • Journal Title: Lung Cancer Volume: 161 Pages: 163-170
  • DOI: 10.1016/j.lungcan.2021.09.011
  • Peer Reviewed / Open Access
• [Journal Article] Highly sensitive fusion detection using plasma cell-free RNA in non-small-cell lung cancers. (2021)
  • Author(s): Hasegawa N, Kohsaka S, Kurokawa K, Shinno Y, Takeda Nakamura I, Ueno T, Kojima S, Kawazu M, Suehara Y, Ishijima M, Goto Y, Kojima Y, Yonemori K, Hayashi T, Saito T, Shukuya T, Takahashi F, Takahashi K, Mano H.
  • Journal Title: Cancer Sci Volume: 112 Issue: 10 Pages: 4393-4403
  • DOI: 10.1111/cas.15084
  • Peer Reviewed / Open Access
• [Journal Article] Comprehensive functional evaluation of variants of fibroblast growth factor receptor genes in cancer. (2021)
  • Author(s): Takeda Nakamura I, Kohsaka S, Ikegami M, Ueno T, Li K, Beyett T, Koyama T, Shimizu T, Yamamoto N, Takahashi F, Takahashi K, Eck M, Mano H.
  • Journal Title: NPJ Precision Oncology Volume: 16 Issue: 1 Pages: 66-66
  • DOI: 10.1038/s41698-021-00204-0
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Comprehensive molecular profiling of pulmonary pleomorphic carcinoma (2021)
  • Author(s): Nagano Masaaki、Kohsaka Shinji、Hayashi Takuo、Ueno Toshihide、Kojima Shinya、Shinozaki-Ushiku Aya、Morita Shigeki、Tsuda Masumi、Tanaka Shinya、Shinohara Toshiya、Omori Yuko、Sugaya Fumiko、Kato Hiroaki、Narita Yoshiaki、Nakajima Jun、Suzuki Kenji、Takamochi Kazuya、Mano Hiroyuki
  • Journal Title: npj Precision Oncology Volume: 5 Issue: 1 Pages: 57-57
  • DOI: 10.1038/s41698-021-00201-3
  • Peer Reviewed / Open Access
• [Journal Article] Appropriate use of cancer comprehensive genome profiling assay using circulating tumor DNA. (2021)
  • Author(s): Sunami K, Bando H, Yatabe Y, Naito Y, Takahashi H, Tsuchihara K, Toyooka S, Mimori K, Kohsaka S, Uetake H, Kinoshita I, Komine K, Takeda M, Hayashida T, Tamura K, Nishio K, Yamamoto N; Working Group of a Joint Task Force of Three Academic Societies for the Promotion of Cancer Genomic Medicine.
  • Journal Title: Cancer Sci. Volume: 112(9) Issue: 9 Pages: 3911-3917
  • DOI: 10.1111/cas.15022
  • Peer Reviewed / Open Access
• [Journal Article] Transcription start site-level expression of thyroid transcription factor 1 isoforms in lung adenocarcinoma and its clinicopathological significance. (2021)
  • Author(s): Sano K, Hayashi T, Suehara Y, Hosoya M, Takamochi K, Kohsaka S, Kishikawa S, Kishi M, Saito S, Takahashi F, Kaneko K, Suzuki K, Yao T, Ishijima M, Saito T.
  • Journal Title: J Pathol Clin Res Volume: 7 Issue: 4 Pages: 361-374
  • DOI: 10.1002/cjp2.213
  • Peer Reviewed / Open Access
• [Journal Article] Correction to: The initial assessment of expert panel performance in core hospitals for cancer genomic medicine in Japan (2021)
  • Author(s): Sunami K, Naito Y, Aimono E, Amano T, Ennishi D, Kage H, Kanai M, Komine K, Koyama T, Maeda T, Morita S, Sakai D, Kohsaka S, Tsuchihara K, Yoshino T.
  • Journal Title: Int J Clin Oncol Volume: 26 Issue: 5 Pages: 1007-1007
  • DOI: 10.1007/s10147-021-01897-w
  • Peer Reviewed
• [Journal Article] Development of an optimal protocol for molecular profiling of tumor cells in pleural effusions at single-cell level (2021)
  • Author(s): Takeda Nakamura I, Ikegami M, Hasegawa N, Hayashi T, Ueno T, Kawazu M, Yagishita S, Goto Y, Shinno Y, Kojima Y, Takamochi K, Takahashi F, Takahashi K, Mano H, Kohsaka S
  • Journal Title: Cancer Sci Volume: － Issue: 5 Pages: 2006-2019
  • DOI: 10.1111/cas.14821
  • Peer Reviewed / Open Access
• [Presentation] 大規模データ解析が拓くがんゲノム医療のNext stage (2023)
  • Author(s): 高阪 真路
  • Organizer: 第113 回日本病理学会総会
• [Presentation] 肺腺癌におけるRNA解析の臨床的妥当性・有用性の検討 (2023)
  • Author(s): 寺島 祐樹、池内 洋史、朴 秀煥、上野 敏秀、小島 進也、高持 一矢、高阪 真路
  • Organizer: 第113 回日本病理学会総会
• [Presentation] TOP-Lパネルの開発 (2023)
  • Author(s): 高阪 真路
  • Organizer: 第8回Liquid Biopsy 研究会
• [Presentation] 日本国内固形癌患者における NTRK 融合遺伝子の保有率を調査する後方視的観察研究 (2023)
  • Author(s): 高阪 真路
  • Organizer: 第61回日本癌治療学会学術総会
• [Presentation] 次世代 CGP 検査の幕開け―GenMineTOP への期待― (2023)
  • Author(s): 高阪 真路
  • Organizer: 第61回日本癌治療学会学術総会
• [Presentation] Opening a new era of omics-based medicine (2023)
  • Author(s): 高阪 真路
  • Organizer: 第14 回 国際ゲノム会議
• [Presentation] Liquid Biopsy from bench to bed side (2023)
  • Author(s): 高阪 真路
  • Organizer: 第82日本癌学会学術総会
• [Presentation] 次世代CGP検査が拓く新たながんゲノム医療 (2023)
  • Author(s): 高阪 真路
  • Organizer: 第82日本癌学会学術総会
• [Presentation] 次世代CGP検査の幕開け (2023)
  • Author(s): 高阪 真路
  • Organizer: 第82日本癌学会学術総会
• [Presentation] 膵癌患者の組織とリキッドバイオプシー検体を用いた分子プロファイリングの有用性 (2023)
  • Author(s): 柳垣 充、宇和川 匡、上野 敏秀、今井 健太、高橋 数冴、新井田厚司、恒松 雅、白井 祥睦、春木 孝一郎、古川 賢英、後町 武志、池上 徹、間野 博行、高阪 真路
  • Organizer: 第82日本癌学会学術総会
• [Presentation] J-PDX ライブラリーにおける Short Tandem Repeat 解析による品質管理の有用性検討 (2023)
  • Author(s): 吉野 友美、柳下 薫寛、牛江 千明、大藤 千里、高橋 亜子、高阪 真路、上野 敏秀、濱田 哲暢
  • Organizer: 第82日本癌学会学術総会
• [Presentation] 我が国におけるがんゲノム医療の現状と展望 (2023)
  • Author(s): 高阪真路
  • Organizer: 日本頭頸部外科学会第12回教育セミナー
  • Invited
• [Presentation] ゲノム研究で新しいがん治療法を創る (2023)
  • Author(s): 高阪真路
  • Organizer: WCRW2023
• [Presentation] ゲノム研究で新しいがん治療法を創る (2023)
  • Author(s): 高阪真路
  • Organizer: 第40回分子病理学研究会 クラークシンポジウム
• [Presentation] 日米におけるがん遺伝子プロファイリング検査開発の展望 (2023)
  • Author(s): 高阪真路
  • Organizer: 第56回日本整形外科学会骨・軟部腫瘍学術集会
  • Invited
• [Presentation] がんゲノム研究が拓く新しい医療 (2023)
  • Author(s): 高阪真路
  • Organizer: 第29回日本遺伝性腫瘍学会学術集会
  • Invited
• [Presentation] 我が国におけるがんゲノム医療の現状と展望 (2023)
  • Author(s): 高阪真路
  • Organizer: 第35回日本内分泌外科学会総会
  • Invited
• [Presentation] Exploratory novel biomarker and resistance mechanism of milademetan, an MDM2 inhibitor, in amplified MDM2 intimal sarcoma from an open-label phase 1b/2 trial (NCCH1806/MK004). (2023)
  • Author(s): Takafumi Koyama、Toshio Shimizu、Yuki Kojima、Kazuki Sudo、Hitomi Sumiyoshi Okuma、Tatsunori Shimoi、Hitoshi Ichikawa、Shinji Kohsaka、Akihiko Yoshida、Naoko Matsui、Kenichi Nakamura、Noboru Yamamoto、Kan Yonemori
  • Organizer: 2023 ASCO Annual Meeting
  • Int'l Joint Research
• [Presentation] RNAシークエンスが拓く新たながんゲノム医療と将来展望 (2023)
  • Author(s): 高阪真路
  • Organizer: 第112回日本病理学会総会
• [Presentation] Development of a comprehensive assay for the molecular profiling of cancer by target enrichment from FFPE specimens (2023)
  • Author(s): Shinji Kohsaka
  • Organizer: 2023 Joint Winter Meeting with RSM
  • Int'l Joint Research
• [Presentation] RNA解析が拓く新たながんゲノム医療 (2022)
  • Author(s): 高阪真路
  • Organizer: 第60回日本癌治療学会
• [Presentation] 東大オンコパネル（TOP）を用いたプレシジョンメディシン（先進医療 B） (2022)
  • Author(s): 鹿毛 秀宣、牛久 綾、石垣 和祥、佐藤 悠佑、田辺 真彦、田中 將太、谷川 道洋、渡邊 広祐、高阪 真路、辰野 健二、牛久 哲男、油谷 浩幸、間野 博行、宮川 清、織田 克利
  • Organizer: 第81日本癌学会学術総会
• [Presentation] FGFR 遺伝子変異のがん化能および薬剤感受性に対する網羅的解析 (2022)
  • Author(s): 中村 育子、高阪 真路、上野 敏秀、高橋 史行、高橋 和久、間野博行
  • Organizer: 第81日本癌学会学術総会
• [Presentation] 網羅的薬効予測マーカー探索プラットフォームの構築 (2022)
  • Author(s): 池内 洋史、松野 悠介、池上 政周、小島 進也、大熊 ひとみ、小島 勇貴、米盛 勧、谷田部 恭、吉岡 研一、間野 博行、高阪 真路
  • Organizer: 第81日本癌学会学術総会
• [Presentation] 小児固形がんにおける循環腫瘍 DNA を用いたリキッドバイオプシーの臨床的有用性の検討 (2022)
  • Author(s): 柳垣 充、荒川 歩、上野 敏秀、大熊 ひとみ、池上 徹、間野 博行、高阪 真路
  • Organizer: 第81日本癌学会学術総会
• [Presentation] 遺伝子プロファイリングを目指した Ghost Cytometry によるcirculating tumor cell 分取実験 (2022)
  • Author(s): 伊田 英恵、河村 踊子、長谷川 延彦、上野 敏秀、小山 隆文、米盛 勧、大江 裕一郎、山本 昇、太田 禎生、間野 博行、高阪 真路
  • Organizer: 第81日本癌学会学術総会
• [Presentation] ユーイング肉腫における診断・治療モニタリングツールとしての血漿中の cell-free RNA の可能性 (2022)
  • Author(s): 長谷川 延彦、窪田 大介、高木 辰哉、齋藤 剛、岩田 慎太郎、川井 章、高阪 真路、間野 博行
  • Organizer: 第81日本癌学会学術総会
• [Presentation] 人工微小環境ポリマーアレイによる新規セルフェノミクスの創出とがん層別化法の開発 (2022)
  • Author(s): 椨 康一、高阪 真路、秀 拓一郎、田賀 哲也
  • Organizer: 第81日本癌学会学術総会
• [Presentation] がんゲノム医療におけるRNAシークエンスの活用法 (2022)
  • Author(s): 高阪真路
  • Organizer: 第81日本癌学会学術総会
• [Presentation] シングルセル解析の臨床応用 (2022)
  • Author(s): 高阪真路
  • Organizer: 第7回クリニカルバイオバンク学会シンポジウム
• [Presentation] がんゲノム医療が加速する研究開発 (2022)
  • Author(s): 高阪真路
  • Organizer: 第73回日本電気泳動学会総会
  • Invited
• [Presentation] リキッドバイオプシーの実践 (2022)
  • Author(s): 高阪真路
  • Organizer: 第19回日本婦人科がん会議
  • Invited
• [Presentation] がん遺伝子プロファイリング検査におけるリキッドバイオプシーの最適化 (2022)
  • Author(s): 高阪真路
  • Organizer: 第 63 回日本臨床細胞学会総会
• [Presentation] 循環腫瘍細胞を用いた遺伝子プロファイリング検査の構築 (2022)
  • Author(s): 高阪真路
  • Organizer: 第 63 回日本臨床細胞学会総会
• [Presentation] BRCA機能的スクリーニングとHBOC診療の個別化 (2022)
  • Author(s): 高阪真路
  • Organizer: 第 2 回 JOHBOC 学術総会
  • Invited
• [Presentation] がんゲノム医療におけるリキッドバイオプシーの有用性と現状 (2021)
  • Author(s): 高阪真路
  • Organizer: 第80日本癌学会学術総会
• [Presentation] High throughput functional analysis for the clinical annotation in cancer genome medicine (2021)
  • Author(s): Shinji Kohsaka
  • Organizer: 1stJCA-AACR Precision Cancer Medicine International Conference
  • Int'l Joint Research / Invited
• [Presentation] がんゲノム医療におけるリキッドバイオプシーの有用性と現状 (2021)
  • Author(s): 高阪真路
  • Organizer: 第62回日本臨床細胞学会総会春期大会
  • Int'l Joint Research / Invited
• [Book] がんゲノム病理学 (2021)
  • Author(s): 高阪真路
  • Total Pages: 234
  • Publisher: 文光堂
  • ISBN: 9784830604850