Cross-talks of GSH, mitochondria, RNA m6A modification, NRF2, and p53 between ferroptosis and cuproptosis in HCC: A review.

Hepatocellular carcinoma (HCC) is a common malignant tumor with high morbidity and mortality, as well as poor prognosis. Therefore, it is imperative to explore alternative therapeutic targets for HCC treatment. Ferroptosis and cuproptosis have recently been identified as metal-dependent cell death mechanisms that play significant roles in HCC treatment. This study identified potential cross-talk between ferroptosis and cuproptosis, including the common hub glutathione, common site of occurrence, mitochondria, shared epigenetic modification mode, RNA N6 methyladenosine modification, mutual inhibitor, nuclear factor erythroid 2-related factor 2, and dual regulator, p53. These findings provide a theoretical foundation for the joint induction of HCC cell death and effective inhibition of HCC progression. However, some immune cells are susceptible to ferroptosis or cuproptosis, which may impair or enhance anti-cancer immune function. We propose strategies to target specific targets molecules such as tripartite motif containing 25, ferroptosis suppressor protein 1, and peroxisome proliferator-activated receptor gamma or exploit the unique acidic environment surrounding cancer cells to precisely induce ferroptosis in cancer cells. This approach aims to advance the development of precision medicine for HCC treatment.