Understanding sorafenib-induced ferroptosis and resistance mechanisms: Implications for cancer therapy

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 proferroptotic 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.

Automated summary

Sorafenib is a key first-line treatment for liver cancer with a well-known safety profile. Although novel first-line drugs may have better efficacy, they also have limitations such as worse safety and cost-effectiveness. In addition to inducing apoptosis, Sorafenib can trigger ferroptosis, which has recently been recognized as immunogenic cell death, providing new possibilities for cancer treatment. Resistance to Sorafenib-induced ferroptosis remains a major challenge.