KEIO RESEARCHERS INFORMATION SYSTEM

Career 【 Display / hide 】

Career 【 Display / hide 】

• 2001.04

  -

  2005.03

  慶應義塾大学医学部内科学教室

• 2005.04

  -

  2010.12

  慶應義塾大学医学部内科学（呼吸器）

• 2011.01

  -

  2012.03

  Beth Israel Deaconess Medical Center, Harvard Medical School

• 2012.04

  -

  Present

  慶應義塾大学医学部内科学（呼吸器）

Academic Background 【 Display / hide 】

Academic Background 【 Display / hide 】

• 2001

  慶応義塾大学, 医学部

  Graduated

Academic Degrees 【 Display / hide 】

Academic Degrees 【 Display / hide 】

• 医学博士, 慶應義塾大学, Dissertation

Research Areas 【 Display / hide 】

Research Areas 【 Display / hide 】

• Life Science / Molecular biology (腫瘍生物学)

• Life Science / Cell biology (細胞生物学)

• Life Science / Respiratory medicine (肺癌)

Research Keywords 【 Display / hide 】

Research Keywords 【 Display / hide 】

• オルガノイド

• トランスレーショナル研究

• バイオバンク

• 細胞生物学

• 肺癌

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Papers 【 Display / hide 】

Papers 【 Display / hide 】

• Basal-shift transformation leads to EGFR therapy-resistance in human lung adenocarcinoma.

  Taro Shinozaki, Kazuhiro Togasaki, Junko Hamamoto, Akifumi Mitsuishi, Takahiro Fukushima, Kai Sugihara, Toshiki Ebisudani, Masahiko Okada, Ayaka Saito, Lisa Shigematsu, Hatsuyo Takaoka, Fumimaro Ito, Keiko Ohgino, Kota Ishioka, Kageaki Watanabe, Tsunekazu Hishima, Yutaka Kurebayashi, Katsura Emoto, Hideki Terai, Shinnosuke Ikemura, Ichiro Kawada, Keisuke Asakura, Tomoyuki Hishida, Hisao Asamura, Yuki Ohta, Sirirat Takahashi, Mayumi Oda, Megumu Saito, Mami Matano, Kenzo Soejima, Masayuki Fujii, Koichi Fukunaga, Hiroyuki Yasuda, Toshiro Sato

  Nature communications 16 ( 1 ) 4369 - 4369 2025.12

  　View Summary

  Although EGFR tyrosine kinase inhibitors (EGFR-TKIs) are effective for EGFR-mutant lung adenocarcinoma (LUAD), resistance inevitably develops through diverse mechanisms, including secondary genetic mutations, amplifications and as-yet undefined processes. To comprehensively unravel the mechanisms of EGFR-TKI resistance, we establish a biobank of patient-derived EGFR-mutant lung cancer organoids, encompassing cases previously treated with EGFR-TKIs. Through comprehensive molecular profiling including single-cell analysis, here we identify a subgroup of EGFR-TKI-resistant LUAD organoids that lacks known resistance-related genetic lesions and instead exhibits a basal-shift phenotype characterized by the hybrid expression of LUAD- and squamous cell carcinoma-related genes. Prospective gene engineering demonstrates that NKX2-1 knockout induces the basal-shift transformation along with EGFR-target therapy resistance. Basal-shift LUADs frequently harbor CDKN2A/B loss and are sensitive to CDK4/6 inhibitors. Our EGFR-mutant lung cancer organoid library not only offers a valuable resource for lung cancer research but also provides insights into molecular underpinnings of EGFR-TKI resistance, facilitating the development of therapeutic strategies.

  • Access to Document (DOI)

• An organoid library unveils subtype-specific IGF-1 dependency via a YAP-AP1 axis in human small cell lung cancer.

  Takahiro Fukushima, Kazuhiro Togasaki, Junko Hamamoto, Katsura Emoto, Toshiki Ebisudani, Akifumi Mitsuishi, Kai Sugihara, Taro Shinozaki, Masahiko Okada, Ayaka Saito, Hatsuyo Takaoka, Fumimaro Ito, Lisa Shigematsu, Yuki Ohta, Sirirat Takahashi, Mami Matano, Yutaka Kurebayashi, Keiko Ohgino, Takashi Sato, Ichiro Kawada, Keisuke Asakura, Tomoyuki Hishida, Hisao Asamura, Shinnosuke Ikemura, Hideki Terai, Kenzo Soejima, Mayumi Oda, Masayuki Fujii, Koichi Fukunaga, Hiroyuki Yasuda, Toshiro Sato

  Nature cancer 6 ( 5 ) 874 - 891 2025.05

  　View Summary

  Small cell lung cancer (SCLC) is a devastating disease with limited therapeutic advancements. Although SCLC has recently been classified into four molecular subtypes, subtype-specific therapies are still lacking. Here, we established 40 patient-derived SCLC organoid lines with predominant TP53 and RB1 alterations and rare targetable genetic lesions. Transcriptome profiling divided the SCLC organoids into neuroendocrine (NE)-type SCLC and non-NE-type SCLC, with the latter characterized by YAP1 or POU2F3 expression. NE-type SCLC organoids grew independent of alveolar niche factors, whereas non-NE-type SCLC organoids relied on insulin-like growth factor (IGF)-1-driven YAP1 and AP1 activation. Therapeutic targeting of IGF-1, YAP1 and AP1 effectively suppressed the growth of non-NE-type organoids. Co-knockout of TP53 and RB1 in human alveolar cells altered their lineage toward the airway epithelium-like fate and conferred IGF-1 dependency, validating the subtype-phenotype connection. Our SCLC organoid library represents a valuable resource for developing biology-based therapies and has the potential to reshape the drug discovery landscape.

  • Access to Document (DOI)

• Initial single-institutional experience with salvage surgery for stage IV non-small-cell lung cancer.

  Tomoyuki Hishida, Naoyuki Oka, Kaito Yano, Seiji Omura, Yu Okubo, Kyohei Masai, Kaoru Kaseda, Keiko Ohgino, Hideki Terai, Hiroyuki Yasuda, Keisuke Asakura

  Interdisciplinary cardiovascular and thoracic surgery 40 ( 3 )  2025.03

  　View Summary

  The purpose of this study was to assess surgical outcomes of salvage surgery for clinical stage IV non-small-cell lung cancer. A total of 14 patients who underwent lung resection following systemic therapy between 2010 and 2022 were included in this study. Systemic therapy prior to surgery included agents including epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in eight patients and non-TKI agents in six (chemotherapy alone: four, chemotherapy plus immune checkpoint inhibitors: two). During a median follow-up of 5.2 years, the EGFR-TKI group showed a favourable 5-year overall survival of 83%; however, it was due to treatment after relapse, and there were no 4-year relapse-free survivors. The non-EGFR-TKI group showed a 5-year relapse-free survival of 33%, and 2 patients have survived more than 3 years without any relapse and further treatment. When considering the role of surgery in multimodal treatment for initial c-stage IV non-small-cell lung cancer, salvage surgery following non-TKI therapy (chemotherapy with or without immune checkpoint inhibitor) can be regarded as genuine salvage surgery.

  • Access to Document (DOI)

• Celecoxib prevents malignant progression of smoking-induced lung tumors via suppression of the COX-2/PGE<inf>2</inf> signaling pathway in mice

  Sakurai K., Chubachi S., Miyata J., Hamamoto J., Naganuma T., Shimada T., Otake S., Nakayama S., Irie H., Tsutsumi A., Kameyama N., Hegab A.E., Shimoda M., Terai H., Yasuda H., Kanai Y., Arita M., Fukunaga K.

  Frontiers in Immunology 16   1557790 2025

  　View Summary

  Introduction: Lung cancer is characterized by a poor prognosis and is a significant comorbidity of chronic obstructive pulmonary disease (COPD). Therefore, effective chemopreventive agents are warranted. We evaluated the effects of the cyclooxygenase-2 (COX-2) inhibitor celecoxib on the prevention of lung-carcinoma development using an intermittent smoking-induced lung-carcinoma mouse model. Additionally, we explored COX-2’s role in lipid metabolism. Methods: Male A/J mice were exposed to sham air or mainstream cigarette smoke for 20 weeks. Vehicle or celecoxib was administered via intragastric feeding once daily. Lung tissues were analyzed for tumor nodules and emphysema; the bronchoalveolar lavage fluid was collected for cell counting. COX-2 expression was measured using real-time polymerase chain reaction and western blotting; lipidomic analysis was conducted using liquid chromatography-tandem mass spectrometry. Cell proliferation and colony-forming assays were performed on LA-4 cells to assess the effects of prostaglandins and COX-2 inhibitors. Results: Intermittent smoking exposure increased lung adenomas, adenocarcinomas, and COX-2 expression. Lung adenomas were characterized by abundant COX-2-positive cells. Celecoxib reduced intermittent smoking-induced inflammation, emphysema, and cell counts in the bronchoalveolar lavage fluid and decreased the incidence of lung adenocarcinomas, whereas the total number of observed lung tumors was unchanged. Celecoxib markedly suppressed single-smoke-induced prostaglandin E2 (PGE2) production in the airway. PGE2 increased LA-4 cell viability via the EP4 receptor and promoted colony formation. Discussion: Celecoxib effectively inhibited lung-carcinoma development, inflammation, and emphysema, demonstrating the potential for chemoprevention in smokers and patients with COPD. Further studies on EP4 inhibitors for the prevention of emphysema and lung cancer are warranted.

  • Access to Document (DOI)

• Real-World Efficacy and Safety of Atezolizumab for Advanced Non-Small Cell Lung Cancer in Japan: A Retrospective Multicenter Analysis.

  Masahiko Okada, Keiko Ohgino, Kohei Horiuchi, Koichi Sayama, Daisuke Arai, Mayuko Watase, Keigo Kobayashi, Takeshi Terashima, Kota Ishioka, Masayoshi Miyawaki, Fumio Sakamaki, Keita Masuzawa, Hideki Terai, Hiroyuki Yasuda, Kenzo Soejima, Koichi Fukunaga

  Journal of clinical medicine 13 ( 24 )  2024.12

  ISSN  2077-0383

  　View Summary

  Background/Objectives: Atezolizumab, an immune checkpoint inhibitor (ICI), was used in a phase III clinical trial, i.e., the OAK trial, of previously treated patients with non-small cell lung cancer. We aimed to evaluate the real-world efficacy and safety of atezolizumab in a non-selected population and identify the clinical characteristics that influence its efficacy. Methods: This was a multicenter, retrospective, single-arm observational study. Seventy-four patients with advanced non-small cell lung cancer, who received atezolizumab monotherapy at Keio University and affiliated hospitals in Japan between April 2018 and March 2019, were enrolled. The follow-up period was until 28 February 2024. The efficacy of treatment and adverse events were reviewed retrospectively. Statistical analyses using Pearson's χ2 test, Fisher's exact test, log-rank test, and Student's t-test were performed. Results: The median age of patients was 70 (range, 45-85) years. The overall survival duration was 7.54 (95% confidence interval [CI], 5.14-11.3) months, and the median time to treatment failure (TTF) was 2.00 (95% CI, 1.75-2.54) months. Patients treated with atezolizumab as their first ICI had a longer TTF than those treated with atezolizumab as their second or subsequent ICI (p = 0.04). Conclusions: Atezolizumab may be more effective when used as the first ICI for previously treated patients and may be safely used in elderly patients with non-small cell lung cancer in real-world settings.

  • Access to Document (DOI)

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Papers, etc., Registered in KOARA 【 Display / hide 】

Papers, etc., Registered in KOARA 【 Display / hide 】

• Identification of lung cancer cell-specific dependent genes or signals using lung cancer organoid library

  Yasuda, Hiroyuki

  福澤諭吉記念慶應義塾学事振興基金事業報告集 (福澤基金運営委員会)  2023

• Clarification of signal pathway dependency of lung cancer using lung cancer organoid library

  Yasuda, Hiroyuki

  科学研究費補助金研究成果報告書 2023

• Identification of signal or gene dependency of lung cancer cells using patient-derived lung cancer organoid library

  Yasuda, Hiroyuki

  福澤諭吉記念慶應義塾学事振興基金事業報告集 (福澤基金運営委員会)  2022

• Identification of essential genes or pathways of lung cancer cells using a patient-derived lung cancer organoid library

  Yasuda, Hiroyuki

  福澤諭吉記念慶應義塾学事振興基金事業報告集 (福澤基金運営委員会)  2021

• Establishment of lung cancer and normal lung organoid library

  Yasuda, Hiroyuki

  科学研究費補助金研究成果報告書 2021

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Reviews, Commentaries, etc. 【 Display / hide 】

Reviews, Commentaries, etc. 【 Display / hide 】

• NSCLCにおける1L nivolumab+ipilimumab後の早期進行の解析　LIGHT-NING(Analysis of early progression after 1L nivolumab + ipilimumab in NSCLC: LIGHT-NING)

  戸井 之裕, 今井 久雄, 山口 哲平, 東 公一, 木島 貴志, 岸 一馬, 渡部 聡, 齋藤 春洋, 高島 雄太, 丹保 裕一, 安田 浩之, 畑地 治, 岡田 守人, 佐藤 悠城, 青江 啓介, 大杉 友之, 飛嶋 雄, 堀之内 秀仁, 大江 裕一郎

  肺癌 ((NPO)日本肺癌学会)  64 ( 5 ) 495 - 495 2024.10

  ISSN  0386-9628

• EGFR遺伝子変異陽性肺癌の治療革新と未来展望　EGFR exon 20insの治療薬開発の経緯とこれから

  安田 浩之

  肺癌 ((NPO)日本肺癌学会)  64 ( 5 ) 359 - 359 2024.10

  ISSN  0386-9628

• EGFR遺伝子変異陽性非小細胞肺癌患者の血中セルフリーDNAを用いたエピゲノム解析(Epigenome analysis of cell-free DNA in patient with non-small cell lung carcinoma with EGFR mutation)

  中島 真, 安田 浩之, 松谷 哲行, 田 迎, 藤本 真央, 新井 恵吏, 富樫 亮, 関 順彦, 金井 弥栄

  日本病理学会会誌 ((一社)日本病理学会)  113 ( 1 ) 367 - 367 2024.02

  ISSN  0300-9181

• CGP検査の結果により遺伝カウンセリング推奨となった胸部悪性腫瘍症例の考察

  福島 貴大, 寺井 秀樹, 中村 康平, 川野 竜太郎, 江本 桂, 石川 麻倫, 緒方 暁彦, 高岡 初誉, 齋藤 彩夏, 扇野 圭子, 安田 浩之, 川田 一郎, 副島 研造, 西原 広史, 福永 興壱

  肺癌 ((NPO)日本肺癌学会)  63 ( 5 ) 461 - 461 2023.10

  ISSN  0386-9628

• NKX2-1が規定する肺腺癌のWnt依存性・非依存性(NKX2-1 expression defines Wnt dependency patterns in human lung adenocarcinoma)

  浜本 純子, 江本 桂, 寺井 秀樹, 川田 一郎, 副島 研造, 安田 浩之, 佐藤 俊朗

  日本癌学会総会記事 ((一社)日本癌学会)  82回   1868 - 1868 2023.09

  ISSN  0546-0476

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Research Projects of Competitive Funds, etc. 【 Display / hide 】

Research Projects of Competitive Funds, etc. 【 Display / hide 】

• 治療抵抗性肺癌オルガノイドライブラリーを用いた獲得耐性機構の本態解明

  2025.04

  -

  2028.03

  基盤研究(B), Principal investigator

• 酸素を用いた癌治療法の開発

  2024.06

  -

  2027.03

  挑戦的研究（開拓）, Principal investigator

• 肺癌オルガノイドライブラリーを用いた肺癌シグナル経路異常の解明

  2021.04

  -

  2024.03

  MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (B), Principal investigator

• 肺癌オルガノイドライブラリー統合解析による癌の不均一性の解明と新規治療標的同定

  2020.04

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  2022.03

  日本医療研究開発機構（AMED), 次世代がん医療創生研究事業, Principal investigator

• 肺癌オルガノイドを用いた治療後期肺癌の悪性度の本態解明

  2019.04

  -

  2022.03

  日本医療研究開発機構（AMED）, 革新的がん医療実用化研究事業, No Setting

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Awards 【 Display / hide 】

Awards 【 Display / hide 】

• 武田科学振興財団研究助成金（医学系研究継続助成）

  2019

  Type of Award： Other

• 研究奨励賞　日本肺癌学会

  2018

  Type of Award： Award from Japanese society, conference, symposium, etc.

• 武田科学振興財団研究助成金（医学系研究）

  2016

  Type of Award： Other

• 第55回　日本呼吸器学会　学会奨励賞

  2015

• 日本肺癌学会　若手奨励賞

  2015

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Courses Taught 【 Display / hide 】

Courses Taught 【 Display / hide 】

• PHARMACOLOGY

  2025

• MEDICAL ONCOLOGY

  2025

• LECTURE SERIES, INTERNAL MEDICINE (PULMONOLOGY)

  2025

• CLINICAL CLERKSHIP IN PULMONOLOGY

  2025

• CLINICAL CLERKSHIP IN INTERNAL MEDICINE (PULMONOLOGY)

  2025

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Memberships in Academic Societies 【 Display / hide 】

Memberships in Academic Societies 【 Display / hide 】

• 日本癌治療学会, 

  2021.03

  -

  Present

• 日本癌学会, 

  2020.10

  -

  Present

• International Association for the Study of Lung Cancer, 

  2018.10

  -

  Present

• 日本臨床腫瘍学会, 

  2007.04

  -

  Present

• American Association for Cancer Research, 

  2005.10

  -

  Present

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