Histone Deacetylases-Based Dual Inhibitors: Research Progress Focusing on Non-Small Cell Lung Cancer Therapy

Abstract

Epigenetic regulation plays a pivotal role in the initiation, progression and drug resistance mechanisms of non-small cell lung cancer (NSCLC). As important epigenetic regulatory enzymes, histone deacetylases (HDACs) are aberrantly activated and closely associated with the malignant progression of NSCLC, emerging as highly promising therapeutic targets. Although several HDAC inhibitors have been approved for the treatment of hematological malignancies, their efficacy remains limited in solid tumors, particularly in NSCLC. In recent years, research and development have focused on the design of HDAC-based dual-target inhibitors, which exhibit remarkable advantages including synergistic anti-tumor effects, reversal of drug resistance and reduction of toxic side effects. This review summarizes the current research status and challenges of HDAC dual inhibitors, aiming to provide a reference for the development of novel, highly effective and low-toxic therapeutic agents for NSCLC.