Harnessing traditional medicine and biomarker-driven approaches to counteract Trichostatin A-induced esophageal cancer progression.

The recent study by Chen highlights the paradoxical role of the histone deacetylase inhibitor (HDACi) Trichostatin A (TSA) in esophageal squamous cell carcinoma (ESCC), revealing its promotion of epithelial-mesenchymal transition (EMT) and tumor migration the BRD4/c-Myc/endoplasmic reticulum (ER)-stress pathway. While HDACis are traditionally considered anti-tumor agents, these findings underscore the need for alternative therapeutic strategies. In this commentary, we discuss the potential of traditional medicine-derived compounds, such as berberine, curcumin, and resveratrol, in modulating epigenetic regulators and mitigating TSA-induced oncogenic pathways. Additionally, we emphasize the prognostic significance of histone acetylation markers, particularly acetylated histone H3, which could serve as predictive biomarkers for ESCC progression and HDACi therapy responsiveness. Further, we explore the role of ER stress in tumor aggressiveness and suggest that compounds like quercetin and baicalein, known for their ER stress-alleviating properties, warrant further investigation. Integrating traditional medicine-based interventions with biomarker-driven targeted therapy may enhance ESCC treatment efficacy while minimizing HDACi-associated risks. We advocate for future research focusing on the interplay between epigenetic modulation, natural compounds, and biomarker identification to refine personalized therapeutic strategies for ESCC.