Treating liver cancer through arginine depletion

Liver cancer, the sixth most common cancer globally and the second-leading cause of cancer-related deaths, presents a critical public health threat. Diagnosis often occurs in advanced stages of the disease, aligning incidence with fatality rates. Given that established treatments, such as stereotactic body radiation therapy and transarterial radioembolization, face accessibility and affordability challenges, the emerging focus on cancer cell metabolism, particularly arginine (Arg) depletion, offers a promising research avenue. Arg-depleting enzymes show efficacy against Arg-auxotrophic cancers, including hepatocellular carcinoma (HCC). Thus, in this review, we explore the limitations of current therapies and highlight the potential of Arg depletion, emphasizing various Arg-hydrolyzing enzymes in clinical development. Teaser: While pegylated recombinant human arginase 1 variants have demonstrated efficacy in treating cancers, including hepatocellular carcinoma, their toxicity limitations drive researchers to investigate safer solutions, with fused recombinant human arginase 1 variants emerging as a promising, affordable, effective, and safe option against liver cancer.