Bakrania Anita, To Jeffrey, Zheng Gang, Bhat Mamatha
Toronto General Hospital Research Institute, Toronto, Ontario, Canada.
Ajmera Transplant Program, University Health Network, Toronto, Ontario, Canada.
Gastro Hep Adv. 2023 Jul 20;2(7):948-963. doi: 10.1016/j.gastha.2023.07.012. eCollection 2023.
Hepatocellular carcinoma (HCC) represents a high-fatality cancer with a 5-year survival of 22%. The Wnt/β-catenin signaling pathway presents as one of the most upregulated pathways in HCC. However, it has so far not been targetable in the clinical setting. Therefore, studying new targets of this signaling cascade from a therapeutic aspect could enable reversal, delay, or prevention of hepatocarcinogenesis. Although enormous advancement has been achieved in HCC research and its therapeutic management, since HCC often occurs in the context of other liver diseases such as cirrhosis leading to liver dysfunction and/or impaired drug metabolism, the current therapies face the challenge of safely and effectively delivering drugs to the HCC tumor site. In this review, we discuss how a targeted nano drug delivery system could help minimize the off-target toxicities of conventional HCC therapies as well as enhance treatment efficacy. We also put forward the current challenges in HCC nanomedicine along with some potential therapeutic targets from the Wnt/β-catenin signaling pathway that could be used for HCC therapy. Overall, this review will provide an insight to the current advances, limitations and how HCC nanomedicine could change the landscape of some of the undruggable targets in the Wnt/β-catenin pathway.
肝细胞癌（HCC）是一种高致死性癌症，5年生存率为22%。Wnt/β-连环蛋白信号通路是HCC中上调最为明显的信号通路之一。然而，到目前为止，该信号通路在临床环境中尚无靶向治疗方法。因此，从治疗角度研究这一信号级联反应的新靶点，可能会实现肝癌发生的逆转、延缓或预防。尽管在HCC研究及其治疗管理方面已经取得了巨大进展，但由于HCC常发生于其他肝脏疾病的背景下，如肝硬化导致肝功能障碍和/或药物代谢受损，目前的治疗方法面临着如何安全有效地将药物输送到HCC肿瘤部位的挑战。在这篇综述中，我们讨论了靶向纳米药物递送系统如何有助于将传统HCC治疗的脱靶毒性降至最低，并提高治疗效果。我们还提出了HCC纳米医学目前面临的挑战，以及Wnt/β-连环蛋白信号通路中一些可用于HCC治疗的潜在治疗靶点。总体而言，这篇综述将深入探讨当前的进展、局限性，以及HCC纳米医学如何改变Wnt/β-连环蛋白通路中一些难以成药靶点的现状。
