2009 Fiscal Year Final Research Report
Strategy for the chemoprevention of hepatocellular carcinoma by targeting phosphorylated RXRa
| Project/Area Number |
17015016
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Gifu University |
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Principal Investigator |
MORIWAKI Hisataka Gifu University, 大学院・医学系研究科, 教授 (50174470)
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| Co-Investigator(Kenkyū-buntansha) |
OKANO Yukio 岐阜大学, 大学院・医学系研究科, 教授 (10177066)
TANAKA Takuji 金沢医科大学, 医学部 (40126743)
KOJIMA Souichi 理化学研究所, 分子細胞病態学研究ユニット, 研究ユニットリーダー (10202061)
NISHIGUCHI Shuhei 兵庫医科大学, 医学部, 教授 (10192246)
SHIMIZU Masahito 岐阜大学, 大学院・医学系研究科, 助教 (90402198)
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| Project Period (FY) |
2005 – 2009
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| Keywords | 核内受容体 / 分子標的 / 化学予防 / 肝臓癌 / レチノイド |
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| Research Abstract |
A malfunction of RXRα due to phosphorylation by activation of the Ras/MAPK and PI3K/Akt signaling pathways is profoundly associated with the development of HCC and thus may be a critical target for HCC chemoprevention. A phase II/III trial of acyclic retinoid (ACR), which targets phosphorylated RXRα, to test its effectiveness in preventing second primary HCC in hepatitis C virus-positive patients is currently underway in Japan as a large-scale randomized placebo-controlled trial. In the present study, the combination of ACR plus specific agent, which targets growth factor receptors, the Ras/MAPK and PI3K/Akt signaling pathways, inhibit the RXRα phosphorylation and it may therefore be a promising strategy to prevent the development of HCC. These findings suggest that the inhibition of RXRα phosphorylation and the restoration of its physiological function as a master regulator for nuclear receptors may be a potentially effective strategy for HCC chemoprevention and treatment.
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