Treating liver cancer through arginine depletion

Drug Discov Today. 2024 Apr;29(4):103940. doi: 10.1016/j.drudis.2024.103940. Epub 2024 Mar 6.

Abstract

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.

Keywords: arginine deprivation; fusion protein engineering; liver cancer; pegylation; recombinant human arginase I.

Publication types

  • Review

MeSH terms

  • Arginase / metabolism
  • Arginine / metabolism
  • Carcinoma, Hepatocellular* / drug therapy
  • Humans
  • Liver Neoplasms* / drug therapy

Substances

  • Arginine
  • Arginase