Department of Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
Front Biosci (Landmark Ed). 2011 Jan 1;16(2):759-69. doi: 10.2741/3718.
The prognosis for patients with hepatocellular carcinoma (HCC) is poor and effective prevention strategies are urgently required. Here, we review abnormalities in the expression and function of retinoids and their receptors, and how they play a critical role in the development of HCC. In particular, a malfunction of RXRalpha due to phosphorylation by Ras-MAPK signaling pathway is profoundly associated with liver carcinogenesis and thus may be a promising target for HCC chemoprevention. Acyclic retinoid (ACR), a synthetic retinoid, inhibits Ras-MAPK activation and RXRalpha phosphorylation, thereby suppressing growth in HCC-derived cells. In clinical trials, ACR has been shown to improve patient survival by preventing viral HCC development, a possible manifestation of the concept of "clonal deletion" therapy. "Combination chemoprevention" with ACR as the key drug has great potential to become an effective strategy for the prevention of liver carcinogenesis. In summary, both basic and clinical research strongly suggest that ACR plays a critical role in preventing the development of HCC and that "clonal deletion" therapy is one of the most practical approaches for this purpose.
肝细胞癌（HCC）患者的预后较差，因此迫切需要有效的预防策略。在这里，我们回顾了视黄酸及其受体表达和功能的异常，以及它们在 HCC 发展中所起的关键作用。特别是，由于 Ras-MAPK 信号通路的磷酸化导致的 RXRalpha 功能障碍与肝癌的发生有很深的关联，因此可能是 HCC 化学预防的一个很有前途的靶点。无环视黄酸（ACR）是一种合成的视黄酸，可抑制 Ras-MAPK 的激活和 RXRalpha 的磷酸化，从而抑制 HCC 衍生细胞的生长。临床试验表明，ACR 通过预防病毒相关性 HCC 的发生来提高患者的生存率，这可能是“克隆删除”治疗概念的一种表现。以 ACR 为关键药物的“联合化学预防”具有很大的潜力成为预防肝癌发生的有效策略。总之，基础和临床研究都强烈表明，ACR 在预防 HCC 的发生中起着关键作用，“克隆删除”治疗是实现这一目标的最实用方法之一。
