Exploration of the Molecular Biological Characteristics of Advanced Colorectal Cancer Suitable for Sequential Therapy
Project/Area Number |
19K07787
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 50020:Tumor diagnostics and therapeutics-related
|
Research Institution | Kawasaki Medical School |
Principal Investigator |
|
Co-Investigator(Kenkyū-buntansha) |
永坂 岳司 川崎医科大学, 医学部, 准教授 (30452569)
谷岡 洋亮 川崎医科大学, 医学部, 講師 (40775491)
堅田 洋佑 川崎医科大学, 医学部, 助教 (20716881)
|
Project Period (FY) |
2019-04-01 – 2023-03-31
|
Project Status |
Completed (Fiscal Year 2022)
|
Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
|
Keywords | 大腸がん / 化学療法 / 逐次治療 / オキサリプラチン / MGMT / メチル化 / バイオマーカー / 逐次療法 / 悪性腫瘍 / 腫瘍遺伝学 / 大腸癌 / 腫瘍検査学 |
Outline of Research at the Start |
「オキサリプラチンを用いた逐次療法と併用療法にBevacizumabを加え比較検討を行った無作為ランダム化第III相臨床試験(C-cubed study)」の参加者から得られた大腸癌組織を対象に、Genetic/Epigenetic変異、TIL/HLA class I発現の有無等、免疫疲弊の解析を行い、大腸癌進展速度の推定が可能となるMolecular subtypeの同定を試みる。
|
Outline of Final Research Achievements |
In our investigation, we propose that MGMT methylation has potential to be a predictive biomarker for recurrence in pStage III colorectal cancer, but not as a prognostic or therapeutic effectiveness marker for unresectable colorectal cancer under chemotherapy. This contradiction is explained by our hypothesis that, while tumors with MGMT methylation experience heightened immunogenicity and augmented antitumor effects under chemotherapy, advanced stages of the cancer may induce an immune exhaustion. Upcoming Mutational Signature analyses will probe further into this observation, specifically whether a noticeable increase in G to A transitions post-chemotherapy in MGMT-methylated tumors may indicate a potential efficacy of subsequent immune checkpoint inhibitor treatments.
|
Academic Significance and Societal Importance of the Research Achievements |
本研究では、MGMTメチル化がpStage III大腸癌の再発予測マーカーとなる可能性を示し、個々の患者の再発リスクを早期に評価する新たな道筋を開いた。しかし、切除不能大腸癌の化学療法に対する予後・効果予測マーカーとはならず、この矛盾が免疫疲弊と関連する可能性を示唆。これは癌治療への新規アプローチを促進し、特にMGMTメチル化を有する腫瘍における化学療法後の免疫チェックポイント阻害剤の有効性を予見する新たな可能性も示唆している。
|
Report
(5 results)
Research Products
(18 results)
-
-
-
-
[Journal Article] Phase 3 trial of sequential versus combination treatment in colorectal cancer: The C-cubed study2022
Author(s)
Ryo Inada, Takeshi Nagasaka, Mototsugu Shimokawa, Hitoshi Ojima, Shingo Noura, Hiroaki Tanioka, Yoshinori Munemoto, Yasuhiro Shimada, Keiichiro Ishibashi, Yoshiaki Shindo, Hideyuki Mishima, Masasumi Okajima, Yoshiyuki Yamaguchi
-
Journal Title
European Journal of Cancer
Volume: 169
Pages: 166-178
DOI
Related Report
Peer Reviewed / Open Access
-
-
[Journal Article] Concordance of acquired mutations between metastatic lesions and liquid biopsy in metastatic colorectal cancer.2021
Author(s)
Taniguchi F, Nyuya A, Toshima T, Yasui K, Mori Y, Okawaki M, Kishimoto H, Umeda Y, Fujiwara T, Tanioka H, Yamaguchi Y, Goel A, Nagasaka T.
-
Journal Title
Future Sci OA.
Volume: 7 (10)
Issue: 10
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
[Journal Article] Clinical and epigenetic features of colorectal cancer patients with somatic POLE proofreading mutations.2021
Author(s)
Kawai T, Nyuya A, Mori Y, Tanaka T, Tanioka H, Yasui K, Toshima T, Taniguchi F, Shigeyasu K, Umeda Y, Fujiwara T, Okawaki M, Yamaguchi Y, Goel A, Nagasaka T.
-
Journal Title
Clin Epigenetics.
Volume: 13 (1)
Issue: 1
Pages: 117-117
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
[Journal Article] A phase II study of FOLFOXIRI plus bevacizumab as initial chemotherapy for patients with untreated metastatic colorectal cancer: TRICC1414 (BeTRI)2021
Author(s)
Shinozaki, K. Yamada, T. Nasu, J. Matsumoto, T. Yuasa, Y. Shiraishi, T. Nagano, H. Moriyama, I. Fujiwara, T. Miguchi, M. Yoshida, R. Nozaka, K. Tanioka, H. Nagasaka, T. Kurisu, Y. Kobayashi, M. Tsuchihashi, K. Inukai, M. Kikuchi, T. Nishina, T.
-
Journal Title
Int J Clin Oncol
Volume: 26
Issue: 2
Pages: 399-408
DOI
Related Report
Peer Reviewed / Open Access
-
-
[Journal Article] The PVT1 lncRNA is a novel epigenetic enhancer of MYC, and a promising risk-stratification biomarker in colorectal cancer2020
Author(s)
Shigeyasu, K. Toden, S. Ozawa, T. Matsuyama, T. Nagasaka, T. Ishikawa, T. Sahoo, D. Ghosh, P. Uetake, H. Fujiwara, T. Goel, A.
-
Journal Title
Mol Cancer
Volume: 1
Issue: 1
Pages: 155-155
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
-
-
-
[Presentation] Genetic 変異情報と Epigenetic 変異情報の融合による新機軸大腸癌 Precision Medicine2019
Author(s)
永坂岳司, 入谷光洋, 鶴田淳, 渡邊裕策, 峯田修明, 母里淑子, 重安邦俊, 楳田祐三, 岸本浩行, 上野富雄, 山口佳之
Organizer
第74回日本大腸肛門病学会学術集会
Related Report
-
[Presentation] Randomized phase III study of sequential treatment with capecitabine or 5-fluorouracil (FP) plus bevacizumab (BEV) followed by the addition with oxaliplatin (OX) versus initial combination with OX+FP+ BEV in the first-line chemotherapy for metastatic colorectal cancer: The C-cubed study2019
Author(s)
T. Nagasaka, R. Inada, H. Ojima, S. Noura, H. Tanioka, Y. Munemoto, Y. Shimada, K. Ishibashi, Y. Shindo, Y. Kagawa, A. Tomibayashi, K. Okamoto, A. Tsuji, Y. Tsuji, S. Yamaguchi, A. SAWAKI, H. Mishima, M. Shimokawa, M. Okajima, Y. Yamaguchi
Organizer
ESMO Congress 2019
Related Report
Int'l Joint Research
-