非環式レチノイドによる肝発がん予防の臨床開発ならびに基礎的作用メカニズムについての研究

概要

論文の詳細を見る
Prognosis of liver cancer is poor due to a high recurrence rate, which is attributable to multicentric carcinogenesis in the liver under exposure to hepatitis virus infection or alcohol intoxication. To overcome such carcinogenesis, deletion of transformed premalignant cellular clone(s) is essential. Since these clones are invisible by medical imaging, pharmacological approach is required. Such a concept of clonal deletion by chemical compounds is defined as cancer chemoprevention. Retinoid X receptor (RXR) is a key nuclear receptor and regulates cellular differentiation and programmed cell death. In liver carcinogenesis, RXR is phosphorylated and loses its transcription activity, leading to cellular atypia and immortalization. Acyclic retinoid is a synthetic RXR-ligand, restores the RXR malfunction, and actually induces differentiation and apoptosis in liver cancer cells. Phase II/III clinical trials of acyclic retinoid demonstrated significant preventive effect on second primary liver carcinogenesis. Currently the phase III trial is in progress with the scheduled key-open in 2016-7. (150 words)
2012-12-25