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 TGFβ, one of the most promising targets of the HCC microenvironment.
肝癌，主要为肝细胞癌（HCC），在全球范围内发病率位居第六，癌症相关死亡率位列第三。HCC的风险因素包括非病毒性肝炎、酒精滥用、环境暴露及遗传因素。目前尚无明确的特定基因改变被证实与HCC肿瘤发生直接相关。当前的标准疗法包括手术选择、全身化疗以及激酶抑制剂，如索拉非尼和瑞戈非尼。针对免疫检查点的免疫疗法代表了一条前景广阔的治疗途径。美国食品药品监督管理局批准的检查点抑制剂，如阿特珠单抗和帕博利珠单抗，已显示出疗效，而联合疗法进一步增强了临床反应。尽管如此，肝细胞癌的治疗仍面临挑战，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有效性。本综述探讨了当前及先进的HCC治疗方法，涵盖了已知及新的潜在靶点，特别是源自蛋白质组学分析的靶点，该分析目前被视为最具前景的研究方向。在探索新策略方面，本文讨论了抗体药物偶联物（ADCs）、嵌合抗原受体T细胞疗法（CAR-T）以及工程化抗体。随后，报告了对肿瘤细胞中过度表达的主要配体/受体对及分子通路的系统分析，并强调了其潜力与局限性。最后，文章讨论了TGFβ，这是HCC微环境中最具潜力的靶点之一。
Hepatocellular Carcinoma: Old and Emerging Therapeutic Targets
肿瘤(癌症)患者之家