The incidence of hepatocellular carcinoma (HCC) is increasing, and 40% of patients are diagnosed at advanced stages. Over the past 5 years, the number of clinically available treatments has dramatically increased for HCC, making patient management particularly complex. Immune checkpoint inhibitors (ICIs) have improved the overall survival of patients, showing a durable treatment benefit over time and a different response pattern with respect to tyrosine kinase inhibitors (TKIs). Although there is improved survival in responder cases, a sizeable group of patients are primary progressors or are ineligible for immunotherapy. Indeed, patients with nonviral etiologies, such as nonalcoholic steatohepatitis (NASH), and alterations in specific driver genes might be less responsive to immunotherapy. Therefore, improving the comprehension of mechanisms of drug resistance and identifying biomarkers that are informative of the best treatment approach are required actions to improve patient survival. Abundant evidence indicates that noncoding RNAs (ncRNAs) are pivotal players in cancer. Molecular mechanisms through which ncRNAs exert their effects in cancer progression and drug resistance have been widely investigated. Nevertheless, there are no studies summarizing the synergistic effect between ncRNA-based strategies and TKIs or ICIs in the preclinical setting. This review aims to provide up-to-date information regarding the possible use of ncRNAs as therapeutic targets in association with molecular-targeted agents and immunotherapies and as predictive tools for the selection of optimized treatment options in advanced HCCs.
肝细胞癌（HCC）的发病率持续上升，其中40%的患者确诊时已处于晚期。过去五年间，临床上可用的HCC治疗方案数量显著增加，这使得患者管理变得尤为复杂。免疫检查点抑制剂（ICIs）改善了患者的总体生存率，显示出随时间推移的持久治疗获益，且其应答模式与酪氨酸激酶抑制剂（TKIs）存在差异。尽管应答者生存期有所延长，但仍有相当一部分患者出现原发性进展或不适合接受免疫治疗。事实上，非病毒性病因（如非酒精性脂肪性肝炎NASH）及特定驱动基因突变的患者可能对免疫治疗反应较弱。因此，深入理解耐药机制并鉴定能指导最佳治疗策略的生物标志物，是提高患者生存率的必要举措。大量证据表明非编码RNA（ncRNAs）在癌症中发挥关键作用。ncRNAs在癌症进展和耐药性中的作用机制已得到广泛研究，但目前尚无研究系统总结临床前模型中ncRNA策略与TKIs或ICIs的协同效应。本综述旨在提供最新信息，探讨ncRNAs作为治疗靶点与分子靶向药物及免疫疗法联用的可能性，并评估其作为预测工具在晚期HCC优化治疗方案选择中的应用前景。
肿瘤(癌症)患者之家