Hepatocellular carcinoma (HCC) is the deadliest emergent health issue around the globe. The stronger oncogenic effect, proteins, and weakened immune response are precisely linked with a significant prospect of developing HCC. Several conventional systemic therapies, antiangiogenic therapy, and immunotherapy techniques have significantly improved the outcomes for early-, intermediate-, and advanced-stage HCC patients, giving new hope for effective HCC management and prolonged survival rates. Innovative therapeutic approaches beyond conventional treatments have altered the landscape of managing HCC, particularly focusing on targeted therapies and immunotherapies. The advancement in HCC treatment suggested by the Food and Drug Administration is multidimensional treatment options, including multikinase inhibitors (sorafenib, lenvatinib, regorafenib, ramucirumab, and cabozantinib) and immune checkpoint inhibitors (atezolizumab, pembrolizumab, durvalumab, tremelimumab, ipilimumab, and nivolumab), in monotherapy and in combination therapy to increase life expectancy of HCC patients. This review highlights the efficacy of multikinase inhibitors and immune checkpoint inhibitors in monotherapy and combination therapy through the analysis of phase II, and III clinical trials, targeting the key molecular pathways involved in cellular signaling and immune response for the prospective treatment of advanced and unresectable HCC and discusses the upcoming combinations of immune checkpoint inhibitors-tyrosine kinase inhibitors and immune checkpoint inhibitors-vascular endothelial growth factor inhibitors. Finally, the hidden challenges with pharmacological therapy for HCC, feasible solutions for the future, and implications of possible presumptions to develop drugs for HCC treatment are reported.
肝细胞癌（HCC）是全球范围内最致命的突发性健康问题。其较强的致癌效应、相关蛋白表达以及减弱的免疫反应，均与HCC的高发病风险密切相关。多种传统全身疗法、抗血管生成疗法及免疫治疗技术已显著改善早、中、晚期HCC患者的预后，为有效控制HCC及提高长期生存率带来新希望。超越传统治疗模式的创新疗法，特别是靶向治疗与免疫治疗，正在改变HCC的治疗格局。美国食品药品监督管理局推荐的HCC治疗进展体现在多维度的治疗方案上，包括多激酶抑制剂（索拉非尼、仑伐替尼、瑞戈非尼、雷莫芦单抗和卡博替尼）与免疫检查点抑制剂（阿特珠单抗、帕博利珠单抗、度伐利尤单抗、曲美木单抗、伊匹木单抗和纳武利尤单抗），通过单药或联合治疗提升HCC患者的预期寿命。本综述通过分析II期和III期临床试验，重点探讨多激酶抑制剂与免疫检查点抑制剂在单药及联合治疗中对晚期不可切除HCC的疗效，这些疗法针对细胞信号传导和免疫应答中的关键分子通路；同时讨论了免疫检查点抑制剂-酪氨酸激酶抑制剂及免疫检查点抑制剂-血管内皮生长因子抑制剂等新兴联合疗法的前景。最后，本文报告了HCC药物治疗中存在的潜在挑战、未来可行的解决方案，以及对开发HCC治疗药物的可能假设及其意义。
Hepatocellular Carcinoma: Beyond the Border of Advanced Stage Therapy
肿瘤(癌症)患者之家