Differential responses to CDV treatment of HPV
+ tumor cells and immortalized keratinocytes versus PHKs and proposed CDV selectivity mechanism. Incorporation of CDV during DNA synthesis leads to DNA damage signaling and elevated p53 levels. Distinct responses are elicited depending on the cell type and p53 status. Normal keratinocytes activate cell cycle regulation mechanisms that allow DNA repair by means of homologous recombination, leading to genomic stability and cell survival. Despite blocking cell cycle progression, HPV- immortalized cells are not able to activate a DNA repair mechanism, while HPV+ tumor cells lack cell cycle regulation and DNA repair due to E6 and E7 oncoproteins. The inability to repair DNA damage leads to genomic instability and activation of apoptosis in these cells. Altered cell cycle regulation and/or DNA damage repair pathways are cited, with their relevant genes marked in red when upregulated and in green when downregulated.