Purinosomes as a therapeutic target in hepatocellular carcinoma: insights and opportunities

Discov Oncol. 2025 Apr 18;16(1):564. doi: 10.1007/s12672-025-02366-w.

Abstract

The formation of purinosomes, dynamic complexes involved in de novo purine biosynthesis, has been recognized as a critical process for cell growth. Although their upregulation in cancer cells suggests their potential as a therapeutic target, the specific role of purinosomes in hepatocellular carcinoma (HCC) remains uncertain. The purinosome score was found to have prognostic value. Enrichment analyses indicated a connection between purinosome-related genes and cell cycle regulation. Moreover, our research has demonstrated a correlation between the upregulation of genes associated with purinosomes and the enhanced formation of purinosomes in Huh-7 cells. Pyrimethamine has been identified as a promising therapeutic option for targeting purinosome to exert anti-cancer effects. Furthermore, the purinosome score exhibited an positive relationship with the response to immunotherapy. It may guide the stratification of liver cancer patients and screen for populations that may benefit from immunotherapy. This study examines the prognostic and predictive value of purinosome in liver cancer, suggesting that targeting purinosome formation with pyrimethamine or immunotherapy could benefit patients with high purinosome scores.

Keywords: Cell cycle; Liver cancer; Prognosis; Purinosome; Therapeutic target.