Hepatocellular carcinoma (HCC) stands as a formidable global health challenge due to its prevalence, marked by high mortality and morbidity rates. This cancer type exhibits a multifaceted etiology, prominently linked to viral infections, non-alcoholic fatty liver disease, and genomic mutations. The inherent heterogeneity of HCC, coupled with its proclivity for developing drug resistance, presents formidable obstacles to effective therapeutic interventions. Autophagy, a fundamental catabolic process, plays a pivotal role in maintaining cellular homeostasis, responding to stressors such as nutrient deprivation. In the context of HCC, tumor cells exploit autophagy, either augmenting or impeding its activity, thereby influencing tumorigenesis. This comprehensive review underscores the dualistic role of autophagy in HCC, acting as both a pro-survival and pro-death mechanism, impacting the trajectory of tumorigenesis. The anti-carcinogenic potential of autophagy is evident in its ability to enhance apoptosis and ferroptosis in HCC cells. Pertinently, dysregulated autophagy fosters drug resistance in the carcinogenic context. Both genomic and epigenetic factors can regulate autophagy in HCC progression. Recognizing the paramount importance of autophagy in HCC progression, this review introduces pharmacological compounds capable of modulating autophagy—either inducing or inhibiting it, as promising avenues in HCC therapy.

中文翻译：

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研究肝细胞癌中的自噬和复杂的细胞机制：强调细胞死亡机制串扰

肝细胞癌（HCC）因其患病率高、死亡率和发病率高而成为一项严峻的全球健康挑战。这种癌症类型表现出多方面的病因，与病毒感染、非酒精性脂肪肝和基因组突变密切相关。 HCC 固有的异质性，加上其产生耐药性的倾向，给有效的治疗干预带来了巨大的障碍。自噬是一种基本的分解代谢过程，在维持细胞稳态、应对营养缺乏等应激源方面发挥着关键作用。在 HCC 中，肿瘤细胞利用自噬，增强或阻碍其活性，从而影响肿瘤发生。这篇全面的综述强调了自噬在 HCC 中的双重作用，它既是一种促生存又是促死亡的机制，影响着肿瘤发生的轨迹。自噬的抗癌潜力体现在其增强肝癌细胞凋亡和铁死亡的能力。相应地，自噬失调会在致癌情况下促进耐药性。基因组和表观遗传因素都可以调节 HCC 进展中的自噬。认识到自噬在 HCC 进展中的至关重要性，本综述介绍了能够调节自噬（诱导或抑制自噬）的药理学化合物，作为 HCC 治疗的有希望的途径。