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Establishment of prediction system for RTK/KRAS targeting therapy in gastric cancer using early response biomarker.

Research Project

Project/Area Number 18K15283
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 50020:Tumor diagnostics and therapeutics-related
Research InstitutionOita University

Principal Investigator

Hirashita Yuka  大分大学, 医学部, 医員 (70771955)

Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywordsバイオマーカー / 感受性予測 / 感受性マーカー / RTK/KRASシグナル / 胃癌 / 大腸癌 / 進行胃癌 / 感受性 / マーカー / 分子標的治療 / オルガノイド / RTK/KRAS / 分子標的薬
Outline of Final Research Achievements

Gastric cancer (GC) and is characterized by genomic alteration with RTK and KRAS signaling pathway, therefore, targeting of the RTK/KRAS downstream pathways could help to broaden the applicability of molecular targeted therapy for GC. We established patient-derived GC organoid (additionally CRC organoid) to analyze the sensitivities of organoids to MEK inhibitor treatment. Furthermore, we showed that the change in pS6 level after MEK inhibition was well correlated with responsiveness to trametinib. We proposed predict system with patient-derived organoids, the change in pS6 could be a useful biomarker for RTK/KRAS signal targeting therapy.

Academic Significance and Societal Importance of the Research Achievements

癌ゲノム時代を迎え、遺伝子異常を標的とした個別化医療が可能となった。しかし遺伝子異常だけでは、分子標的治療薬の感受性が完全に予測できずより精度の高いバイオマーカーが望まれている。
本研究では癌オルガノイドを用いて薬剤投与早期のタンパク質リン酸化レベルの変化による感受性予測法は、癌オルガノイドを用いた従来の感受性試験と比べ、少量の検体量でより早期に検出可能であった。またKRASなどの遺伝子変異だけでは予測不可能な耐性を示す症例も見つけることが可能であった。申請者の示す予測法は遺伝子異常と組み合わせることで、RTK/KRASシグナル標的治療において、より精度の高い感受性予測法の一助になると考える。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (18 results)

All 2021 2020 2019

All Journal Article (12 results) (of which Peer Reviewed: 12 results,  Open Access: 10 results) Presentation (6 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Differences in Regression Patterns of Complete and Incomplete Intestinal Metaplasia at Ten Years after <i>Helicobacter pylori</i> Eradication2021

    • Author(s)
      Wada Yasuhiro、Kodama Masaaki、Mizukami Kazuhiro、Okimoto Tadayoshi、Fuchino Takafumi、Tsutsumi Koshiro、Fukuda Masahide、Hirashita Yuka、Fukuda Kensuke、Okamoto Kazuhisa、Ogawa Ryo、Kushima Ryoji、Murakami Kazunari
    • Journal Title

      ACTA HISTOCHEMICA ET CYTOCHEMICA

      Volume: 54 Issue: 6 Pages: 185-194

    • DOI

      10.1267/ahc.21-00069

    • NAID

      130008132648

    • ISSN
      0044-5991, 1347-5800
    • Year and Date
      2021-12-24
    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Immunohistochemical differences in gastric mucosal damage between nodular and non-nodular gastritis caused by <i>Helicobacter pylori</i> infection2021

    • Author(s)
      Okamoto K, Kodama M, Mizukami K, Okimoto T, Abe H, Ogawa R, Fukuda F, Matsunari O, Hirashita Y, Wada Y, Fukuda M, Murakami K
    • Journal Title

      Journal of Clinical Biochemistry and Nutrition

      Volume: 69 Issue: 2 Pages: 216-221

    • DOI

      10.3164/jcbn.20-179

    • NAID

      130008082423

    • ISSN
      0912-0009, 1880-5086
    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Gastric mucosal changes, and sex differences therein, after Helicobacter pylori eradication: A long-term prospective follow-up study.2021

    • Author(s)
      Kodama M, Okimoto T, Mizukami K, Hirashita Y, Wada Y, Fukuda M, Matsunari O, Okamoto K, Ogawa R, Fukuda K, Kudo Y, Kawahara Y, Murakami K.
    • Journal Title

      J Gastroenterol Hepatol

      Volume: - Issue: 8 Pages: 2210-2216

    • DOI

      10.1111/jgh.15477

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Early response in phosphorylation of ribosomal protein S6 is associated with sensitivity to trametinib in colorectal cancer cells2021

    • Author(s)
      Hirashita Yuka、Tsukamoto Yoshiyuki、Kudo Y、Kakisako D、Kurogi S、Hijiya Naoki、Nakada C、Uchida T、Hirashita T、Hiratsuka T、Akagi T、Ueda Y、Shiroshita H、Etoh T、Mizukami K、Honda K、Okimoto T、Kodama M、Inomata M、Moriyama Masatsugu、Murakami K
    • Journal Title

      Laboratory Investigation

      Volume: - Issue: 8 Pages: 1036-1047

    • DOI

      10.1038/s41374-021-00590-w

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Complex polypectomy in the sigmoid colon using a double-balloon endolumenal intervention platform2021

    • Author(s)
      Huang A.、Hirashita T.、Urakawa S.、Hirashita Y.、Alzghari T.、Milsom J. W.
    • Journal Title

      Techniques in Coloproctology

      Volume: 25 Issue: 5 Pages: 599-600

    • DOI

      10.1007/s10151-020-02400-9

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] α ‐Tocopherol suppresses hepatic steatosis by increasing CPT‐1 expression in a mouse model of diet‐induced nonalcoholic fatty liver disease2020

    • Author(s)
      Tokoro Masanori、Gotoh Koro、Kudo Yoko、Hirashita Yuka、Iwao Masao、Arakawa Mie、Endo Mizuki、Oribe Junya、Masaki Takayuki、Honda Koichi、Kakuma Tetsuya、Seike Masataka、Murakami Kazunari、Shibata Hirotaka
    • Journal Title

      Obesity Science & Practice

      Volume: 7 Issue: 1 Pages: 91-99

    • DOI

      10.1002/osp4.460

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] S6 ribosomal protein phosphorylation is associated with malignancy of intraductal papillary mucinous neoplasm of the pancreas.2020

    • Author(s)
      Hirashita T, Hirashita Y, Iwashita Y, Endo Y, Kiyonaga M, Matsumoto S, Hijiya N, Moriyama M, Murakami K, Inomata M.
    • Journal Title

      Ann Gastroenterol Surg

      Volume: 4 Issue: 5 Pages: 571-579

    • DOI

      10.1002/ags3.12367

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Influence of acotiamide on <sup>13</sup>C-urea breath test for <i>Helicobacter pylori</i> diagnosis2020

    • Author(s)
      Mizukami Kazuhiro、Katsuta Makoto、Okamoto Kazuhisa、Fukuda Kensuke、Ogawa Ryo、Kawahara Yoshinari、Hirashita Yuka、Sato Yuto、Fukuda Masahide、Okimoto Tadayoshi、Kodama Masaaki、Fujioka Toshio、Murakami Kazunari
    • Journal Title

      Journal of Clinical Biochemistry and Nutrition

      Volume: 67 Issue: 3 Pages: 332-337

    • DOI

      10.3164/jcbn.20-17

    • NAID

      130007934182

    • ISSN
      0912-0009, 1880-5086
    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Examine the Availability and Safety of Mucosal Cutting Biopsy Technique for Diagnosis of Gastric Submucosal Tumor.2019

    • Author(s)
      Mizukami K, Matsunari O, Ogawa R, Hirashita Y, Okamoto K, Fukuda K, Sonoda A, Akiyama H, Ozaka S, Kawahara Y, Okimoto T, Kodama M, Murakami K.
    • Journal Title

      Gastroenterol Res Pract

      Volume: 3121695 Pages: 1-6

    • DOI

      10.1155/2019/3121695

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Evaluation of a Novel Anti-H. pylori Antibody Detection Kit by Latex Turbidimetric Immunoassay.2019

    • Author(s)
      Kodama M, Okimoto T, Mizukami K, Fukuda K, Ogawa R, Okamoto K, Matsunari O, Wada Y, Hirashita Y, Murakami K.
    • Journal Title

      Clin Lab

      Volume: 65 Issue: 06/2019 Pages: 929-936

    • DOI

      10.7754/clin.lab.2018.180918

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Differences in <i>Helicobacter pylori</i> and CagA antibody changes after eradication between subjects developing and not developing gastric cancer2019

    • Author(s)
      Kodama M, Okimoto T, Mizukami K, Fukuda K, Ogawa R, Okamoto K, Matsunari O, Kawahara Y, Hirashita Y, Murakami K.
    • Journal Title

      Journal of Clinical Biochemistry and Nutrition

      Volume: 65 Issue: 1 Pages: 71-75

    • DOI

      10.3164/jcbn.19-30

    • NAID

      130007672120

    • ISSN
      0912-0009, 1880-5086
    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Endoscopic gastric mucosal atrophy as a predictor of colorectal polyps: a large scale case-control study2019

    • Author(s)
      Kawahara Y, Kodama M, Mizukami K, Saito T, Hirashita Y, Sonoda A, Fukuda K, Matsunari O, Okamoto K, Ogawa R, Okimoto T, Murakami K.
    • Journal Title

      Journal of Clinical Biochemistry and Nutrition

      Volume: 65 Issue: 2 Pages: 153-159

    • DOI

      10.3164/jcbn.19-47

    • NAID

      130007700225

    • ISSN
      0912-0009, 1880-5086
    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 研究生活を通して感じること2021

    • Author(s)
      平下 有香
    • Organizer
      第107回日本消化器病学会総会 キャリア支援委員会企画
    • Related Report
      2021 Annual Research Report
  • [Presentation] eEF1A dimethylation level in the basal area of Helicobacter pylori-eradicated gastric mucosa is associated with the risk of gastric cancer2021

    • Author(s)
      平下有香 兒玉雅明 村上和成
    • Organizer
      2021年10月第80回癌学会学術総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 除菌後胃粘膜におけるeEF1Aジメチル化と胃癌発症との相関2020

    • Author(s)
      平下 有香
    • Organizer
      第92回日本胃癌学会総会
    • Related Report
      2020 Research-status Report
  • [Presentation] Dimethylation level of eEF1A and the gastric mucosa after Helicobacter pylori (H. pylori) eradication therapy2020

    • Author(s)
      Yuka Hirashita
    • Organizer
      American College of Gastroenterology 2020
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] RAS/BRAF変異型 進行大腸癌における早期反応性マーカーを用いたtrametinib感受性予測法の検討2019

    • Author(s)
      平下 有香
    • Organizer
      第27回日本消化器関連学会週間
    • Related Report
      2019 Research-status Report
  • [Presentation] 膵IPMN癌化・浸潤過程におけるmTORC1活性と糖の取り込みとの相関2019

    • Author(s)
      平下 有香
    • Organizer
      第114回日本消化器病学会 九州支部例会
    • Related Report
      2019 Research-status Report

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Published: 2018-04-23   Modified: 2023-01-30  

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