Research Centers and Institutes, Health Center Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine (Hiyoshi)


Associate Professor (Non-tenured)

External Links

Career 【 Display / hide

  • 1998.05

    慶應義塾大学医学部, 内科学教室, 研修医

  • 2000.05

    埼玉県立循環器・呼吸器病センター, 内科, 専修医

  • 2001.06

    東京歯科大学市川総合病院, 内科, 助手

  • 2002.06

    慶應義塾大学医学部, 呼吸循環器内科, 助手

  • 2005.07

    日野市立病院, 内科, 主任医員

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Academic Background 【 Display / hide

  • 1992.04

    慶應義塾大学, 医学部

    University, Graduated

Academic Degrees 【 Display / hide

  • 学士(医学), Keio University, Coursework, 1998.03

  • 博士(医学), Keio University, Dissertation, 2009.02


Licenses and Qualifications 【 Display / hide

  • 医師免許, 1998.05

  • 日本内科学会 認定内科医, 2002.09

  • 日本内科学会 総合内科専門医, 2006.12

  • 日本内科学会 指導医, 2006.09

  • 日本内科学会 JMECCインストラクター, 2015.12

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Research Areas 【 Display / hide

  • Life Science / Respiratory medicine


Books 【 Display / hide

  • インフルエンザ診療マニュアル

    Kawada Ichiro, 南江堂, 2001.01

    Scope: インフルエンザと社会

Papers 【 Display / hide

  • Genotype-phenotype mapping of a patient-derived lung cancer organoid biobank identifies NKX2-1-defined Wnt dependency in lung adenocarcinoma

    Ebisudani T., Hamamoto J., Togasaki K., Mitsuishi A., Sugihara K., Shinozaki T., Fukushima T., Kawasaki K., Seino T., Oda M., Hanyu H., Toshimitsu K., Emoto K., Hayashi Y., Asakura K., Johnson T.A., Terai H., Ikemura S., Kawada I., Ishii M., Hishida T., Asamura H., Soejima K., Nakagawa H., Fujii M., Fukunaga K., Yasuda H., Sato T.

    Cell Reports (Cell Reports)  42 ( 3 )  2023.03

     View Summary

    Human lung cancer is a constellation of tumors with various histological and molecular properties. To build a preclinical platform that covers this broad disease spectrum, we obtained lung cancer specimens from multiple sources, including sputum and circulating tumor cells, and generated a living biobank consisting of 43 lines of patient-derived lung cancer organoids. The organoids recapitulated the histological and molecular hallmarks of the original tumors. Phenotypic screening of niche factor dependency revealed that EGFR mutations in lung adenocarcinoma are associated with the independence from Wnt ligands. Gene engineering of alveolar organoids reveals that constitutive activation of EGFR-RAS signaling provides Wnt independence. Loss of the alveolar identity gene NKX2-1 confers Wnt dependency, regardless of EGFR signal mutation. Sensitivity to Wnt-targeting therapy can be stratified by the expression status of NKX2-1. Our results highlight the potential of phenotype-driven organoid screening and engineering for the fabrication of therapeutic strategies to combat cancer.

  • Population Pharmacokinetics, Pharmacogenomics, and Adverse Events of Osimertinib and its Two Active Metabolites, AZ5104 and AZ7550, in Japanese Patients with Advanced Non-small Cell Lung Cancer: a Prospective Observational Study

    Ishikawa E., Yokoyama Y., Chishima H., Kasai H., Kuniyoshi O., Kimura M., Hakamata J., Nakada H., Suehiro N., Nakaya N., Nakajima H., Ikemura S., Kawada I., Yasuda H., Terai H., Jibiki A., Kawazoe H., Soejima K., Muramatsu H., Suzuki S., Nakamura T.

    Investigational New Drugs (Investigational New Drugs)  41 ( 1 ) 122 - 133 2023.02

    ISSN  01676997

     View Summary

    Background: Potential novel strategies for adverse event (AE) management of osimertinib therapy, including therapeutic drug monitoring and the use of biomarkers, have not yet been fully investigated. This study aimed to evaluate (1) the relationship between exposure to osimertinib, especially its active metabolites (AZ5104 and AZ7550), and AEs, and (2) the relationship between germline polymorphisms and AEs. Methods: We conducted a prospective, longitudinal observational study of 53 patients with advanced non-small cell lung cancer receiving osimertinib therapy from February 2019 to April 2022. A population pharmacokinetic model was developed to estimate the area under the serum concentration–time curve from 0 to 24 h (AUC0–24) of osimertinib and its metabolites. Germline polymorphisms were analyzed using TaqMan® SNP genotyping and CycleavePCR® assays. Results: There was a significant association between the AUC0–24 of AZ7550 and grade ≥ 2 paronychia (p = 0.043) or anorexia (p = 0.011) and between that of osimertinib or AZ5104 and grade ≥ 2 diarrhea (p = 0.026 and p = 0.049, respectively). Furthermore, the AUC0–24 of AZ5104 was significantly associated with any grade ≥ 2 AEs (p = 0.046). EGFR rs2293348 and rs4947492 were associated with severe AEs (p = 0.019 and p = 0.050, respectively), and ABCG2 rs2231137 and ABCB1 rs1128503 were associated with grade ≥ 2 AEs (p = 0.008 and p = 0.038, respectively). Conclusion: Higher exposures to osimertinib, AZ5104, and AZ7550 and polymorphisms in EGFR, ABCG2, and ABCB1 were related to higher severity of AEs; therefore, monitoring these may be beneficial for osimertinib AE management.

  • Most Important Things and Associated Factors With Prioritizing Daily Life in Patients With Advanced Lung Cancer

    Kameyama N., Sato T., Arai D., Fujisawa D., Takeuchi M., Nakachi I., Kawada I., Yasuda H., Ikemura S., Terai H., Nukaga S., Nakano Y., Hirano T., Minematsu N., Asakura T., Kamatani T., Tanaka K., Suzuki S., Miyawaki M., Naoki K., Fukunaga K., Soejima K.

    JCO Oncology Practice (JCO Oncology Practice)  18 ( 12 ) E1977 - E1986 2022.12

    ISSN  26881527

     View Summary

    PURPOSE:Patients' values and priorities in their lives should be appreciated from an early phase of incurable diseases such as advanced cancer. However, studies examining these characteristics have been lacking. This study attempted to determine what patients with advanced lung cancer valued most, once they had been diagnosed, and any associated factors.METHODS:Patients with newly diagnosed advanced lung cancer (N = 248) were enrolled in a questionnaire survey conducted at 16 hospitals in Japan. Their priorities were assessed using a free-text response to the question what is the most important thing to you now? at the time of diagnosis and 3 months after diagnosis. The free-text responses were classified into 10 categories for quantification. The clinical characteristics associated with the category describing daily life were further examined.RESULTS:Free-text comments were obtained from 103 (44.0%) and 66 (42.6%) patients at the time of diagnosis and at 3 months, respectively. The most frequent categories were family (at diagnosis: 50.5%; at 3 months: 50.0%) and daily life (at diagnosis: 33.0%; at 3 months: 36.4%), followed by health (at diagnosis: 32.0%; at 3 months: 27.3%) at both time points. The patients mentioning daily life, the issues related to how to spend daily life, showed significantly higher total scores and functional well-being subscale scores on the Functional Assessment of Cancer Therapy-Lung scale at both time points and lower depression scores at diagnosis and lower anxiety scores at 3 months on the Hospital Anxiety and Depression Scale.CONCLUSION:Family and daily life were highly valued by patients with advanced lung cancer at diagnosis. A better quality of life and better mood were associated with mentioning daily life, which should be taken into account in care planning to maintain patients' involvement in daily life even with incurable diseases.

  • Real-world clinical practice for advanced non-small-cell lung cancer in the very elderly: A retrospective multicenter analysis

    Fukushima T., Oyamada Y., Ikemura S., Nukaga S., Inoue T., Arai D., Ohgino K., Kuroda A., Ishioka K., Sakamaki F., Suzuki Y., Terai H., Yasuda H., Kawada I., Fukunaga K., Soejima K.

    Clinical Lung Cancer (Clinical Lung Cancer)  23 ( 6 ) 532 - 541 2022.09

    ISSN  15257304

     View Summary

    Background: The optimal treatment for advanced non-small cell lung cancer (NSCLC) in very elderly patients is unclear. We aimed to evaluate their treatment in real-world clinical practice and identify suitable therapy that can improve their prognosis. Materials and methods: The medical records of 132 Japanese patients aged 80 years and older with advanced NSCLCs who were enrolled at a university hospital and its 9 affiliates were retrospectively analyzed. Clinical characteristics and overall survival (OS) were compared based on the Eastern Cooperative Oncology Group Performance Status (ECOG PS) and biomarker statuses. Patients were defined as biomarker-positive if programmed death-ligand 1 tumor proportion score (PD-L1 TPS) was ≥ 50% or activating mutations were present in epidermal growth factor receptor, anaplastic lymphoma kinase, or c-ros oncogene 1. Finally, the factors contributing to better prognosis were explored in both PS 0 - 2 and PS 3 - 4 patient groups. Results: The PS 0 - 2 patients showed a longer median OS than the PS 3 - 4 patients (5.5 vs. 1.6 months). PS 0 - 2 patients with positive biomarkers who received chemotherapy showed a significantly longer median OS than those without (18.1 vs. 3.7 months). Among the biomarker-negative/unknown PS 0 - 2 patients, the median OS showed no significant difference between those who received chemotherapy and those who did not (4.5 vs. 3.1 months). The multivariate analysis showed that treatment with tyrosine kinase inhibitors or immune checkpoint inhibitors was related to better prognoses in the PS 0 - 2 group. Conclusion: Biomarker-matched therapy is effective even in very elderly patients. Meanwhile, the effectiveness of chemotherapy for biomarker-negative/unknown PS 0 - 2 patients is questionable.

  • Long-Term Treatment-Free Survival After Multimodal Therapy in a Patient with Stage IV Lung Adenocarcinoma

    Takaoka H., Terai H., Emoto K., Shigematsu L., Ito F., Saito A., Okada M., Ohgino K., Ikemura S., Yasuda H., Nakachi I., Kawada I., Fukunaga K., Soejima K.

    OncoTargets and Therapy (OncoTargets and Therapy)  15   981 - 989 2022

     View Summary

    We report the first case of a patient with non-small cell lung cancer (NSCLC) with malignant pleural effusion (MPE) who achieved disease-and treatment-free survival for nearly 10 years. A 50-year-old man was diagnosed with NSCLC with MPE and underwent chemotherapy and salvage thoracic surgery. The patient received chemotherapy with cisplatin, pemetrexed, and bevacizumab, and a partial response was achieved. After informed consent was obtained from the patient, right middle lobectomy was performed to achieve local tumor control. Postoperative adjuvant chemotherapy with pemetrexed and bevacizumab was discontinued after almost 1 year of chemotherapy due to side effects such as diarrhea and muscle weakness. The patient has survived without recurrence of lung cancer for more than 11 years after being diagnosed and nearly 10 years after discontinuing chemotherapy.

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Reviews, Commentaries, etc. 【 Display / hide

Presentations 【 Display / hide

  • NHBE肺癌発生モデルにおける癌抑制遺伝子、癌遺伝子のメチル化、および脱メチル化の定量的検討


    第44回日本肺癌学会総会 (東京) , 


    Oral presentation (general)

  • DNAメチル転移酵素3b(DNMT3b)の癌化における重要性


    第44回日本肺癌学会総会 (東京) , 


    Oral presentation (general)

  • 癌化いおけるde novo DNAメチル転移酵素、DNMT3b1/3b2の機能的差異の検討−実験モデルの確立−


    第44回日本肺癌学会総会 (東京) , 


    Oral presentation (general)

  • 癌化におけるDNAメチルトランスフェラーゼ(DNMT3b)の重要性

    Soejima Kenzou, Kawada Ichirou, Watanabe Hideo, Fujishima Seitarou, Yamaguchi Kazuhiro



    Oral presentation (general)

  • NHBE肺癌発生モデルを用いた不死化,癌化過程における局所的メチル化および全体的低メチル化の検討

    Watanabe Hideo, Soejima Kenzou, Kawada Ichirou, Yamaguchi Kazuhiro



    Oral presentation (general)

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

  • 悪性胸膜中皮腫におけるMET遺伝子異常の解明と新薬の個別化治療への臨床応用


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

Awards 【 Display / hide

  • 研究奨励賞(Respiratory Research Award)

    2014.11, 第18回東京呼吸病態研究会, 非小細胞肺癌とMET遺伝子異常, RON遺伝子異常

    Type of Award: Other


Courses Taught 【 Display / hide











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Courses Previously Taught 【 Display / hide

  • 内科学、血液ガス、酸塩基平衡

    Keio University


    Autumn Semester, Lecture