p53 pathway and its potential targeted therapeutic approach
Project/Area Number |
19K07645
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 50010:Tumor biology-related
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Research Institution | Sapporo Medical University |
Principal Investigator |
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Project Period (FY) |
2019-04-01 – 2023-03-31
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Project Status |
Completed (Fiscal Year 2022)
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Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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)
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Keywords | がん抑制遺伝子 / p53 / 長鎖非コードRNA / TP53 |
Outline of Research at the Start |
p53は悪性腫瘍で最も高頻度に変異しているが,「がん抑制遺伝子」であるためp53を分子標的とした治療薬の開発は遅れている.本研究ではp53による転写ネットワークの全貌を解明し,p53による細胞死誘導に相互作用する経路を探索して,変異型p53と合成致死(synthetic lethality)に関与する経路および正常型p53によるアポトーシス誘導を増強する経路を明らかにして,そのメカニズム解明および革新的な根本的治療の開発につながる研究を展開する.また,p53変異をもつ腫瘍で発現上昇している標的遺伝子などを同定し,癌治療に有望な分子標的阻害薬の開発につながる基礎研究を展開する.
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Outline of Final Research Achievements |
The development of anti-cancer drugs targeting the p53 pathway has been slow because p53 is a "tumor suppressor gene", although p53 is the most frequently mutated gene in human malignancies. We found that the lncRNA NEAT1 is a direct transcriptional target of p53, and that a long non-coding RNA, lnc53AC, expression affects the translational level and post-translational modifications of p53 and is involved in the reduction of p53 protein expression.
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Academic Significance and Societal Importance of the Research Achievements |
NEAT1は正常型p53遺伝子が存在する場合にのみ腫瘍抑制作用を発揮し,逆に,p53の機能が正常でない場合には,NEAT1ががんの進行を促進する可能性さえあることがわかった.がんにおけるNEAT1の役割を解明する重要な手がかりとなる. 大腸がんにおけるlnc53AC高発現群は,全生存率のみならず,無病生存率,疾患特異的生存率,無増悪生存率においても有意に予後不良であり,p53活性を制御するoncogenic lncRNAであることを明らかにした.lnc53ACは新しい分子標的治療薬の有力候補となる可能性がある.
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Report
(5 results)
Research Products
(31 results)
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[Journal Article] Early dynamics of circulating tumor DNA predict chemotherapy responses for patients with esophageal cancer2021
Author(s)
Ryosuke Fujisawa , Takeshi Iwaya, Fumitaka Endo, Masashi Idogawa, Noriyuki Sasaki, Hayato Hiraki, Shoichiro Tange, Tomomi Hirano, Yuka Koizumi , Masakazu Abe, Tomoko Takahashi, Mizunori Yaegashi , Yuji Akiyama, Mari Masuda, Akira Sasaki, Fumiaki Takahashi, Yasushi Sasaki, Takashi Tokino, Satoshi S Nishizuka
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Journal Title
Carcinogenesis
Volume: 42(10)
Issue: 10
Pages: 1239-1249
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Genetic analyses of a secondary poroma and trichoblastoma in a HRAS-mutated sebaceous nevus2021
Author(s)
Minowa, Tomoyuki ; Kamiya, Takafumi ; Hida, Tokimasa ; Okura, Masae ; Kato, Junji ; Idogawa, Masashi ; Tange, Shoichiro ; Hirano, Tomomi ; Tokino, Takashi ; Uhara, Hisashi,
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Journal Title
J Dermatol
Volume: 48
Issue: 8
Pages: 1268-1272
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Significance of gene mutations in the Wnt signaling pathway in traditional serrated adenomas of the colon and rectum2020
Author(s)
Nakanishi, H. Sawada, T. Kaizaki, Y. Ota, R. Suzuki, H. Yamamoto, E. Aoki, H. Eizuka, M. Hasatani, K. Takahashi, N. Inagaki, S. Ebi, M. Kato, H. Kubota, E. Kataoka, H. Takahashi, S. Tokino, T. Minamoto, T. Sugai, T. Sasaki, Y.
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Journal Title
PLoS One
Volume: 15
Issue: 2
Pages: e0229262-e0229262
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Chemotherapy after progression on nivolumab is essential for responders with genetic alterations of driver gene: Review of two recurrent/metastatic oral squamous cell carcinoma patients2020
Author(s)
Ogi, K. Kobayashi, J. Nakagaki, T. Okamoto, J. Koike, K. Hirokawa, N. Someya, M. Sakamoto, H. Takada, K. Tokino, T. Sasaki, Y. Hiratsuka, H. Miyazaki, A.
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Journal Title
Oral Oncol
Volume: 102
Pages: 104509-104509
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Pathogenesis of multiple pancreatic cancers involves multicentric carcinogenesis and intrapancreatic metastasis2020
Author(s)
Fujita, Y. Matsuda, S. Sasaki, Y. Masugi, Y. Kitago, M. Yagi, H. Abe, Y. Shinoda, M. Tokino, T. Sakamoto, M. Kitagawa, Y.
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Journal Title
Cancer Sci
Volume: 111
Issue: 2
Pages: 739-748
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] FGFR Signaling as a Candidate Therapeutic Target for Cancers Resistant to Carbon Ion Radiotherapy2019
Author(s)
Darwis, N. D. M. Nachankar, A. Sasaki, Y. Matsui, T. Noda, S. E. Murata, K. Tamaki, T. Ando, K. Okonogi, N. Shiba, S. Irie, D. Kaminuma, T. Kumazawa, T. Anakura, M. Yamashita, S. Hirakawa, T. Kakoti, S. Hirota, Y. Tokino, T. Iwase, A. Ohno, T. Shibata, A. Oike, T. Nakano, T.
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Journal Title
Int J Mol Sci
Volume: 20
Issue: 18
Pages: 4563-4563
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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