肿瘤细胞治疗研究
英文原题：Hepatocellular Carcinoma: Old and Emerging Therapeutic Targets.
肝癌，主要是肝细胞癌（HCC），在全球发病率中排名第六，在癌症相关死亡中排名第三。
肝癌，主要是肝细胞癌（HCC），在全球发病率中排名第六，在癌症相关死亡中排名第三。HCC 的危险因素包括非病毒性肝炎、酒精滥用、环境暴露和遗传因素。没有明确的特定遗传改变与 HCC 肿瘤发生直接相关。当前的标准疗法包括手术方案、全身化疗和激酶抑制剂，如索拉非尼和瑞戈非尼。针对免疫检查点的免疫治疗代表了一条有前景的途径。FDA 批准的检查点抑制剂，如 atezolizumab 和 pembrolizumab，显示出疗效，联合疗法增强了临床反应。尽管如此，肝细胞癌（HCC）的治疗仍然是一个挑战，因为复杂的肿瘤生态系统及其相关的免疫抑制微环境阻碍了现有治疗方法的疗效。本综述探讨了当前和先进的 HCC 治疗方法，考虑了已知和新的潜在靶点，特别是来自蛋白质组学分析的靶点，这目前被认为是最有前景的方法。在探索新策略方面，本综述讨论了抗体药物偶联物（ADCs）、CAR-T 细胞疗法（CAR-T）和工程化抗体。然后报告了对肿瘤细胞中报道过表达的主要配体/受体对和分子通路的系统分析，强调了它们的潜力和局限性。最后，讨论了 TGF，这是 HCC 微环境中最有前景的靶点之一。
Liver cancer, predominantly hepatocellular carcinoma (HCC), globally ranks sixth in incidence and third in cancer-related deaths. HCC risk factors include non-viral hepatitis, alcohol abuse, environmental exposures, and genetic factors. No specific genetic alterations are unequivocally linked to HCC tumorigenesis. Current standard therapies include surgical options, systemic chemotherapy, and kinase inhibitors, like sorafenib and regorafenib. Immunotherapy, targeting immune checkpoints, represents a promising avenue. FDA-approved checkpoint inhibitors, such as atezolizumab and pembrolizumab, show efficacy, and combination therapies enhance clinical responses. Despite this, the treatment of hepatocellular carcinoma (HCC) remains a challenge, as the complex tumor ecosystem and the immunosuppressive microenvironment associated with it hamper the efficacy of the available therapeutic approaches. This review explores current and advanced approaches to treat HCC, considering both known and new potential targets, especially derived from proteomic analysis, which is today considered as the most promising approach. Exploring novel strategies, this review discusses antibody drug conjugates (ADCs), chimeric antigen receptor T-cell therapy (CAR-T), and engineered antibodies. It then reports a systematic analysis of the main ligand/receptor pairs and molecular pathways reported to be overexpressed in tumor cells, highlighting their potential and limitations. Finally, it discusses TGF , one of the most promising targets of the HCC microenvironment.
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