State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Industrial Microbiology, Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, National and Local United Engineering Lab of Metabolic Control Fermentation Technology, China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science & Technology, Tianjin, 300457, China.
State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Industrial Microbiology, Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, National and Local United Engineering Lab of Metabolic Control Fermentation Technology, China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science & Technology, Tianjin, 300457, China.
Eur J Med Chem. 2021 Nov 15;224:113690. doi: 10.1016/j.ejmech.2021.113690. Epub 2021 Jul 5.
Liver cancer most commonly develops in patients with chronic liver disease, the etiology of which includes viral hepatitis (B and C), alcohol, obesity, dietary carcinogens, and so forth. The current treatment modalities, including surgical resection and liver transplantation, have been found far from effective. Hence, there is an obvious critical need to develop alternative strategies for the treatment of it. In this review, we discuss the formation process and therapeutic targets of liver cancer. Currently, targeted therapy is limited to sorafenib, lenvatinib, regorafenib, ramucirumab and cabozantinib which leads to a survival benefit in patients, but on the other hand is hampered by the occurrence of drug resistance. Pleasingly and importantly, there are multiple natural products undergoing clinical evaluation in liver cancer, such as polyphenols like icaritin, resveratrol, and silybin, saponins including ginsenoside Rg3 and glycyrrhizinate, alkaloid containing irinotecan and berberine and inorganic compound arsenic trioxide at present. Preclinical and clinical studies have shown that these compounds inhibit liver cancer formation owing to the influence on the anti-viral, anti-inflammation, anti-oxidant, anti-angiogenesis and anti-metastasis activity. Furthermore, a series of small molecule derivatives inspired by the aforementioned compounds are designed and synthesized according to structure-activity relationship studies. Drug combination and novel type of drug-targeted delivery system thereof have been well developed. This article is ended by a perspective remark of futuristic development of natural product-based therapeutic regimen for liver cancer treatment. We expect that this review is an account for current status of natural products as promising anti-liver cancer treatments and should contribute to its understanding.
肝癌最常发生于慢性肝病患者中，其病因包括病毒性肝炎（B 型和 C 型）、酒精、肥胖、饮食性致癌剂等。目前的治疗方法，包括手术切除和肝移植，已被证明远远不够有效。因此，显然迫切需要开发治疗肝癌的替代策略。在这篇综述中，我们讨论了肝癌的形成过程和治疗靶点。目前，靶向治疗仅限于索拉非尼、仑伐替尼、瑞戈非尼、雷莫芦单抗和卡博替尼，这些药物可使患者受益，但另一方面又受到耐药性的限制。令人高兴的是，也有多种天然产物正在进行肝癌的临床评估，如多酚类如淫羊藿素、白藜芦醇和水飞蓟素，皂苷类如人参皂苷 Rg3 和甘草酸，生物碱类如伊立替康和小檗碱，无机化合物三氧化二砷等。临床前和临床研究表明，这些化合物通过影响抗病毒、抗炎、抗氧化、抗血管生成和抗转移活性来抑制肝癌的形成。此外，还根据构效关系研究设计和合成了一系列受上述化合物启发的小分子衍生物。药物联合及其新型药物靶向递药系统也得到了很好的发展。本文以对未来基于天然产物的肝癌治疗方案的发展前景展望作为结尾。我们希望这篇综述能说明目前天然产物作为有前途的抗肝癌治疗方法的现状，并有助于人们对其的理解。
