Hepatocellular carcinoma (HCC) is the most common type of primary tumor in the liver and is a leading cause of cancer‐related death worldwide. Activated hepatic stellate cells (HSCs) are key components of the HCC microenvironment and play an important role in the onset and progression of HCC through the secretion of growth factors and cytokines. Current treatment modalities that include chemotherapy, radiotherapy and ablation are able to activate HSCs and remodel the tumor microenvironment. Growing evidence has demonstrated that the complex interaction between activated HSCs and tumor cells can facilitate cancer chemoresistance and metastasis. Therefore, therapeutic targeting of activated HSCs has emerged as a promising strategy to improve treatment outcomes for HCC. This review summarizes the molecular mechanisms of HSC activation triggered by treatment modalities, the function of activated HSCs in HCC, as well as the crosstalk between tumor cells and activated HSCs. Pathways of activated HSC reduction are discussed, including inhibition, apoptosis, and reversion to the inactivated state. Finally, we outline the progress and challenges of therapeutic approaches targeting activated HSCs in the development of HCC treatment.

中文翻译：

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肝星状细胞对肝细胞癌的治疗调节剂。

肝细胞癌（HCC）是肝脏中最常见的原发性肿瘤类型，并且是全球癌症相关死亡的主要原因。活化的肝星状细胞（HSC）是HCC微环境的关键组成部分，并通过分泌生长因子和细胞因子在HCC的发生和发展中发挥重要作用。当前的治疗方式包括化学疗法，放射疗法和消融术能够激活HSC并重塑肿瘤微环境。越来越多的证据表明，活化的HSC与肿瘤细胞之间的复杂相互作用可以促进癌症的化学抗性和转移。因此，针对活化的HSC的靶向治疗已经成为改善HCC治疗结果的有希望的策略。这篇综述总结了由治疗方式触发的HSC激活的分子机制，HCC中激活的HSC的功能以及肿瘤细胞与激活的HSC之间的串扰。讨论了激活的HSC减少的途径，包括抑制，凋亡和回复到失活状态。最后，我们概述了在发展HCC治疗中靶向活化HSC的治疗方法的进展和挑战。