Introduction

This invention regards the use of SIRT1 inhibitor or antagonist to prevent or treat human papillomavirus (HPV)-associated diseases. The ultimate goal is to develop treatment de-escalation strategies for HPV-associated cancer using novel combinatorial therapeutic approaches that include SIRT1 inhibitor in association with standard radio- and chemotherapy.

Technical features

Human papillomaviruses (HPV) are widely spread viruses that infect the multilayered squamous epithelia of the genital, cutaneous and upper respiratory tract. They are associated with the development of tumors of the anogenital and head and neck areas, especially oropharynx, where the cellular deacetylase SIRT1 is highly expressed. Notably, we demonstrate that SIRT1 induces the degradation of the tumor suppressor p53 that plays a crucial role in driving HPV-induced cancer. Accordingly, SIRT1 pharmacological inhibition (for example using the drug EX527-Selisistat), leads to p53 restoration. The goal is to develop novel combinatorial therapeutic approaches that include the SIRT1 inhibitor in association with the standard anticancer therapies in order to develop de-escalation strategies that holds the potential to increase the effectiveness of the existing cancer therapies while reducing the side effects.

Possible Applications

• for HPV-associated cancer treatment;
• for HPV-associated disease treatment;
• for HPV-associated disease prevention.

Advantages

• EX527, EU approved orphan drug;
• Minimally invasive therapy and low side effects:
• De-escalation strategies for standard therapy;
• Increase the existing treatment efficacy;
• Restoration of the tumor suppressor p53;
• Inhibition of HPV E6 and E7 oncoprotein expression.