School of Basic Medical Sciences, Southwest Medical University, Luzhou, 646000, Sichuan, China.
Department of Neurosurgery, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China.
Eur J Pharmacol. 2023 Sep 15;955:175913. doi: 10.1016/j.ejphar.2023.175913. Epub 2023 Jul 17.
Sorafenib is an important first-line treatment option for liver cancer due to its well-characterized safety profile. While novel first-line drugs may have better efficacy than Sorafenib, they also have limitations such as worse safety and cost-effectiveness. In addition to inducing apoptosis, Sorafenib can also trigger ferroptosis, which has recently been recognized as an immunogenic cell death, unleashing new possibilities for cancer treatment. However, resistance to Sorafenib-induced ferroptosis remains a major challenge. To overcome this resistance and augment the efficacy of Sorafenib, a wide range of nanomedicines has been developed to amplify its pro-ferroptotic effects. This review highlights the mechanisms underlying Sorafenib-triggered ferroptosis and its resistance, and outlines innovative strategies, particularly nanomedicines, to overcome ferroptosis resistance. Moreover, we summarize molecular biomarkers that signify resistance to Sorafenib-mediated ferroptosis, which can assist in predicting therapeutic outcomes.
索拉非尼因其明确的安全性特征，成为肝癌的重要一线治疗选择。虽然新型一线药物可能比索拉非尼具有更好的疗效，但它们也存在安全性和成本效益较差等局限性。除了诱导细胞凋亡外，索拉非尼还可以触发铁死亡，最近人们认识到铁死亡是一种免疫原性细胞死亡，为癌症治疗带来了新的可能性。然而，索拉非尼诱导的铁死亡耐药性仍然是一个主要挑战。为了克服这种耐药性并增强索拉非尼的疗效，已经开发了广泛的纳米药物来放大其促铁死亡作用。本综述强调了索拉非尼触发铁死亡及其耐药性的机制，并概述了克服铁死亡耐药性的创新策略，特别是纳米药物。此外，我们总结了表明对索拉非尼介导的铁死亡耐药性的分子生物标志物，这些标志物可以帮助预测治疗结果。
