Blog – Page 8

Despite the great technological and medical advances in fighting viral diseases, new therapies for most of them are still lacking, and existing antivirals suffer from major limitations regarding drug resistance and a limited spectrum of activity. In fact, most approved antivirals are directly acting antiviral (DAA) drugs, which interfere with viral proteins and confer great selectivity towards their viral targets but suffer from resistance and limited spectrum. Nowadays, host-targeted antivirals (HTAs) are on the rise, in the drug discovery and development pipelines, in academia and in the pharmaceutical industry. These drugs target host proteins involved in the virus life cycle and are considered promising alternatives to DAAs due to their broader spectrum and lower potential for resistance.

Vitamin A metabolism and signaling through nuclear retinoic acid receptors (RARs α,β,γ) regulate embryogenesis, immune functions, and cell differentiation in most cell types. RARγ is highly expressed in stratified squamous epithelial cells of the oral cavity and skin. While data indicate that RARγ agonism is anti-tumorigenic in oral cavity squamous cell carcinoma (OCSCC), the specific, primary gene targets of RARγ remain poorly characterized. Here, we define RARγ signaling pathways through integrating genome-wide RARγ binding by Cleavage under Targets and Release Using Nuclease (CUT&RUN), chromatin histone marks, and global transcriptomics ± agonists in human OCSCC cells and in human OCSCC cells with deletion of RARG (RARGKO).