Targeting SIRT1 to develop novel combinatorial therapeutic approaches against human papillomavirus-associated cancers

Background Human papillomavirus (HPV)-associated cancers of the genital and head&neck (HN) region represent ~5% of all cancers worldwide and are set to remain a major health concern for the foreseeable future, thereby requiring novel effective therapeutic solutions. Currently, the treatment for these tumors involves radiotherapy, chemotherapy, or surgery, all with devastating effects on the targeted anatomical sites. Thus, alternative antiviral therapies with fewer side effects are urgently needed to improve patient outcomes. Hypothesis We have recently identified the cellular deacetylase SIRT1 as a novel key player in HPV-induced transformation in epithelial cells. More specifically, our preliminary data support the hypothesis that the HPV-induced SIRT1 upregulation is crucial for p53 deacetylation and its ensuing destabilization, thus providing an alternative, attractive, and feasible option to inhibit cancer cell proliferation -also through downregulation of the viral oncoprotein E6 and E7- while increasing the effectiveness of existing anticancer therapies, mainly cisplatin and radiotherapy (national patent application in October 2020).