Letter to the Editor: GEN1 as a potential therapeutic target in gastric cancer

Abstract

I thoroughly reviewed the paper by Zhang et al published in the recent issue of World Journal of Gastrointestinal Oncology, and commend the authors for their in-depth analysis of the oncogenic functions of GEN1 in gastric cancer (GC). The recent work by Zhang et al sheds light on the oncogenic role of GEN1 in GC, which is involved in cell cycle progression, mitochondrial function, ferroptosis, and chemotherapeutic sensitivity. The findings of this study are of scientific interest and future studies to increase the translational relevance of the work are proposed.

Keywords: GEN1; Gastric cancer; Ferroptosis; Mitochondrial dysfunction; Cell cycle; Chemotherapy sensitivity

Core Tip: Gastric cancer (GC) growth is driven by complex molecular pathways including genomic instability, cell cycle dysregulation, mitochondrial dysfunction, and ferroptosis. Novel data suggest that GEN1, a Holliday junction resolvase involved in DNA repair, is a key oncogenic regulator in GC that promotes tumor cell proliferation, migration, survival, and chemoresistance, and modulates ferroptosis-related pathways, suggesting that GEN1 may be a therapeutic target and that adding molecular markers related to DNA damage responses may enhance diagnostic accuracy and therapy stratification in GC.