Histone deacetylase and epidermal growth factor receptor (HDAC/EGFR)

The "HDACs + EGFR signaling" target refers to a dual-therapeutic strategy that combines the inhibition of Histone Deacetylases (HDACs) and the Epidermal Growth Factor Receptor (EGFR). EGFR is a receptor tyrosine kinase that plays a critical role in cell proliferation and survival, and its dysregulation is a hallmark of many solid tumors, particularly non-small cell lung cancer (NSCLC) [Source: NIH/NCI]. HDACs are epigenetic regulators that modify chromatin structure and the activity of various non-histone proteins, influencing gene expression and protein stability [Source: UniProt]. The synergy between these two targets is significant because HDAC inhibition can prevent or reverse resistance to EGFR inhibitors by downregulating compensatory pathways like MET or AXL and inducing apoptosis [Source: PubMed, PMID: 20802022]. This dual approach is often explored through combination therapies or single-molecule multi-target inhibitors like CUDC-101 [Source: PubChem]. Clinically, this strategy aims to enhance anti-tumor activity and overcome the limitations of monotherapy in resistant cancer phenotypes [Source: Journal of Hematology & Oncology].

Other names

HDAC/EGFR dual targetEGFR-HDAC axisHistone deacetylase and Epidermal growth factor receptor signalingEGFR/HDAC inhibitionHDACs + EGFR signaling

The mechanism involves the simultaneous inhibition of EGFR tyrosine kinase activity, which blocks downstream PI3K/AKT and MAPK pathways, and HDAC-mediated deacetylation. HDAC inhibition leads to hyperacetylation of histones and non-histone proteins like HSP90; the latter results in the degradation of EGFR and other client proteins, thereby overcoming resistance mechanisms [Source: Cancer Research, 2010].