Human Papilloma Virus (HPV) is linked to several types of epithelial cancer. Chief among these is cervical cancer, causally linked to HPV infection in 95 percent of cases and a leading cause of death for women worldwide. HPV infection has also been causally implicated in other types of epithelial cancers including roughly 20 percent of head and neck cancers. While prophylactic HPV vaccines exist, there is currently no treatment for those living with HPV, and this leads to 13,000 new cases of cervical cancer in the U.S. each year. Development of HPV therapeutics are critical as five-year relative survival rates in those diagnosed with cervical cancer have not significantly improved in the past 40 years (1).
Dr. Marmorstein has identified a class of compounds that inhibit the ability of HPV associated viral oncoprotein E7 to disrupt pRb/E2F complexes in vitro. Retinoblastoma protein (pRb) normally binds with the E2F family of transcription factors to regulate the cell cycle, differentiation, and apoptosis. When present, HPV-E7 disrupts the pRb/E2F interaction by binding to pRb causing dysregulation of cell cycle entry and neoplasia. HPV-E7 is an attractive drug target and has no human ortholog. The compounds identified by Dr. Marmorstein are the first known class of small molecule inhibitors of the HPV-E7/pRb interaction.
Stage of Development
Preclinical studies with a representative compound of the class demonstrated apoptosis selectively in HPV infected cells as well as a reduction of tumor size in vivo with no observable deleterious effects or toxicity (2). Additional preclinical data is being generated to support the advancement of a lead series.
Issued and pending patent applications covering the class of inhibitors and methods of use. 14/356979.
We are actively seeking a collaboration to help advance our candidates through preclinical development.
- Fera DS et al. Chem Biol. 2012 Apr 20;19(4):518-528. PMID: 22520758