Advances in ferroptosis for castration-resistant prostate cancer treatment: novel drug targets and combination therapy strategies.

Abstract

Background: Metastatic prostate cancer (PCa) has much lower survival and ultimately develops castration resistance, which expects novel targets and therapeutic approaches. As a result of iron-dependent lipid peroxidation, ferroptosis triggers programmed cell death and has been associated with castration-resistant prostate cancer (CRPC).

Subjects: To better understand how ferroptosis can be used to treat CRPC, we reviewed the following: First, ferroptosis mechanisms and characteristics. We then pay attention to ferroptosis effects on CRPC, and the relationship between ferroptosis and CRPC treatment. Finally, we'd like to figure out if ferroptosis could predict the prognosis of CRPC thus screening early for populations that may benefit from appropriate therapies.

Results: The review demonstrated that ferroptosis regulators like PI3K/AKT/mTOR, DECR1 et al., have a significant role in the development of CRPC and that several inducers of ferroptosis, such as erastin, BSO, RSL3, and FIN56, have already demonstrated their effects in that area. What's more, ferroptosis is crucial for radiation-induced anticancer effects by inducing lipid peroxidation and regulating p53, AMPK, and others. Additionally, it has been discovered that certain GPX4 and SLC7A11 inhibitors can increase radiosensitivity, which brings new combination strategies. Finally, among the genes associated with ferroptosis, which may be excellent predictors of prostate cancer prognosis, several risk models have been developed and shown promising predictive capabilities.

Conclusions: Ferroptosis can serve as a potential therapeutic target for CRPC, and could be a new strategy for combination therapy. Moreover, ferroptosis-related genes may be great indicators of PCa prognosis. Further research on ferroptosis in CRPC therapy can benefit from the frameworks provided by this review.