FHIT

The FHIT (Fragile Histidine Triad) gene functions as a tumor suppressor, mediating DNA damage response and apoptosis in epithelial cells^[1]. Mechanistically, FHIT interacts with multiple signaling pathways, including the ATR/Chk1 axis, to regulate cell cycle checkpoints and maintain genomic stability^[2][3]. In disease models, loss of FHIT expression is associated with increased susceptibility to carcinogenesis, particularly in lung, esophageal, and gastrointestinal cancers^[4][5]. Compared with related tumor suppressors, FHIT uniquely localizes at common fragile sites and is frequently inactivated by genomic deletions, distinguishing it from isoforms such as WWOX or VHL^[6][7]. FHIT deficiency promotes accumulation of DNA lesions and genomic instability, facilitating early oncogenic transformation and progression in epithelial tissues^[8]. Experimental studies have employed FHIT restoration and FHIT-mimetic peptides to suppress tumor growth, indicating potential applications for therapeutic intervention^[9][10]. These interventions provide a model to study apoptosis induction, replication stress response, and drug sensitivity in FHIT-deficient tumors^[9][11]. Therefore, FHIT serves as both a biomarker of genomic instability and a functional target for preclinical studies, enabling mechanistic insights into tumor suppressor pathways and informing the development of precision oncology strategies^[12][13].