Epigenetic mechanism of castration resistance prostate cancer in response to tumor microenvironment
| Project/Area Number |
20K18133
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 56030:Urology-related
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| Research Institution | Chiba University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 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 2022: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 去勢抵抗性前立腺癌 / 癌エピゲノム / 低酸素環境 / 前立腺癌 / 微小環境 / 低酸素 |
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| Outline of Research at the Start |
男性罹患数上位の前立腺癌の中で去勢抵抗性前立腺癌（CRPC）への移行は臨床上問題であり、複数のCRPC薬剤が使用可能になった現在も、依然として致死的疾患である。その主因の一つに治療ストレスに付随する腫瘍微小環境への暴露に誘発されたheterogeneityの変化があり、このことが個別化医療への展開を困難としている。そこで本研究では、微小環境が前立腺癌に及ぼすエピゲノム変化を軸に去勢抵抗性獲得の分子機構を同定し、CRPC治療層別化因子の確立を目的とする。
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| Outline of Final Research Achievements |
Castration-resistant prostate cancer is a lethal disease, and one of its main causes is heterogeneity induced by exposure to the tumor microenvironment associated with treatment stress. However, the molecular mechanism is not fully understood. In this study, we focused on the effects of the microenvironment on prostate cancer and the differences in the environmental response, and performed comprehensive epigenomic analysis using prostate cancer cell lines. Our results identified alteration of metabolic profiles after the acquisition of castration resistance, and showed that microenvironment-derived epigenomic changes may influence the acquisition of castration resistance.
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| Academic Significance and Societal Importance of the Research Achievements |
去勢抵抗性前立腺癌における腫瘍微小環境によるheterogeneityの変化については十分に解明されておらず、その分子メカニズムやゲノム変異以外のエピゲノム異常機構については未だ不明な点が多い。本研究はその一端を説明するものであり、微小環境への分子応答機構をゲノム変化や遺伝子発現変化より早期に起こるエピゲノム変化に着目した。治療抵抗性獲得のより早期に、さらに既存の治療戦略とは異なる視点から層別化しうる可能性を秘めており、実臨床において適切な個別化医療の展開へ繋がることが期待される。
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Report
(4 results)
Research Products
(16 results)
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[Journal Article] The heavy chain of 4F2 antigen promote prostate cancer progression via SKP-22021
Author(s)
Maimaiti Maihulan、Sakamoto Shinichi、Sugiura Masahiro、Kanesaka Manato、Fujimoto Ayumi、Matsusaka Keisuke、Xu Minhui、Ando Keisuke、Saito Shinpei、Wakai Ken、Imamura Yusuke、Nakayama Keiichi、Kanai Yoshikatsu、Kaneda Atsushi、Ikehara Yuzuru、Ikeda Jun-Ichiro、Anzai Naohiko、Ichikawa Tomohiko
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Journal Title
Scientific Reports
Volume: 11
Issue: 1
Pages: 11478-11478
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] Relationship between epigenetic and metabolic alterations in castration-resistant prostate cancer2021
Author(s)
Manato Kanesaka, Hiroaki Sato, Masahiro Sugiura, Takayuki Hoshii, Atsushi Okabe, Masaki Fukuyo, Bahityar Rahmutulla Nawai, Shinichi Sakamoto, Akira Komiya, Tomohiko Ichikawa, Atsushi Kaneda
Organizer
The 80th Annual Meeting of the Japanese Cancer Association
Related Report
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[Presentation] Identification of metabolic shift mediated by epigenetic alteration in castration resistant prostate cancer2021
Author(s)
Manato Kanesaka, Takayuki Hoshii, Atsushi Okabe, Hiroaki Sato, Sanji Kanaoka, Masahiro Sugiura, Masaki Fukuyo, Bahityar Rahmutulla Nawai, Shinichi Sakamoto, Akira Komiya, Tomohiko Ichikawa, Atsushi Kaneda
Organizer
The 8th Cancer Epigenomics Symposium
Related Report
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