vorinostat + gefitinib

Vorinostat + gefitinib is an investigational combination therapy consisting of two small molecule drugs with distinct mechanisms of action, evaluated primarily for the treatment of non-small cell lung cancer (NSCLC), including cases with acquired resistance to EGFR-tyrosine kinase inhibitors. Vorinostat is a histone deacetylase inhibitor (HDACI) that modulates gene expression by altering chromatin structure, leading to increased acetylation of histones and affecting transcriptional regulation. Gefitinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that blocks EGFR signaling pathways involved in tumor cell proliferation and survival. The combination has demonstrated synergistic antitumor activity in preclinical models and early-phase clinical studies, particularly by enhancing apoptosis through multiple mechanisms. These include inhibition of the IGF-1R/AKT pathway, ROS-dependent caspase activation, HSP90 cleavage leading to degradation of client proteins such as EGFR, MET, and AKT, and upregulation of pro-apoptotic proteins like BIM. This dual targeting approach aims to overcome resistance mechanisms associated with single-agent EGFR-TKI therapy in NSCLC[1][2][3][4][5].

Brand names

ZolinzaIressa

Other names

vorinostat + gefitinib