Department of Gastrointestinal Medical Oncology, Cancer Hospital of Harbin Medical University, Harbin, 150040, Heilongjiang, People's Republic of China.
Department of Pharmacology (The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin, People's Republic of China.
J Cancer Res Clin Oncol. 2018 Dec;144(12):2329-2337. doi: 10.1007/s00432-018-2740-3. Epub 2018 Aug 22.
Hepatocellular carcinoma (HCC) is a complicated disease with low survival rate due to frequent recurrence and the lack of efficient therapies. For advanced HCC, sorafenib, as the only approved first-line drug for HCC, improves the survival to some extent, but depressingly with severe adverse effects and emerging resistance conditions, which cause a poor prognosis. Ferroptosis is a new recognized way of non-apoptosis-regulated cell death, characterized by the iron-dependent accumulation of lipid hydroperoxides, showing a tremendous promising in the therapy of cancer, especially in HCC. To provide ideas for the diagnosis and treatment of HCC, we summarized the role of ferroptosis in HCC.
The relevant literature from PubMed is reviewed in this article.
Interestingly enough, investigators have found sorafenib can induce ferroptosis in HCC. Moreover, recent researches reported increasing pathways and mechanisms related to ferroptosis in HCC such as TP53 and Rb, and strategies to improve sorafenib resistance by targeting ferroptosis. In addition, other drugs were reported to induce ferroptosis in HCC such as erastin and showed good efficacy in vivo and in vitro.
In this review, we summarize pathways and mechanisms of ferroptosis in HCC and other digestive system neoplasms such as gastric cancer, pancreatic cancer and colorectal cancer and point out the trends of ferroptosis in HCC.
肝细胞癌（HCC）是一种复杂的疾病，由于频繁复发和缺乏有效治疗方法，其生存率较低。对于晚期 HCC，索拉非尼作为唯一批准用于 HCC 的一线药物，在一定程度上提高了生存率，但令人沮丧的是，它具有严重的不良反应和新出现的耐药情况，导致预后较差。铁死亡是一种新发现的非凋亡调控细胞死亡方式，其特征是铁依赖性脂质过氧化物的积累，在癌症治疗中具有巨大的应用前景，特别是在 HCC 中。为了为 HCC 的诊断和治疗提供思路，我们总结了铁死亡在 HCC 中的作用。
本文综述了来自 PubMed 的相关文献。
有趣的是，研究人员发现索拉非尼可以诱导 HCC 发生铁死亡。此外，最近的研究报道了 HCC 中与铁死亡相关的增加途径和机制，如 TP53 和 Rb，并提出了通过靶向铁死亡来提高索拉非尼耐药性的策略。此外，其他药物如 erastin 被报道在 HCC 中诱导铁死亡，并在体内和体外显示出良好的疗效。
在本综述中，我们总结了 HCC 及其他消化系统肿瘤（如胃癌、胰腺癌和结直肠癌）中铁死亡的途径和机制，并指出了铁死亡在 HCC 中的发展趋势。
