Candidate Proteasome Inhibitors that Prevent E6 Mediated p53 Degradation and Selectively Kill HPV+ Cervical Cancer

Abstract (Set) High-risk strains of Human papillomavirus (HPV) cause over 90% of cervical cancers. About 20 million people (men and women) are thought to have an active HPV infection at any given time. Yearly, 14,000 cases are diagnosed and 5,000 women each year die of cervical cancer in the United States. Levels of the tumor suppressor protein p53 were found to be unusually low due to the presence of infection with high-risk or oncogenic strains of HPV. Expression of HPV proteins E6 and E7 promote degradation of p53 via the ubiquitin-proteasome pathway and represents a major mechanism by which virus transforms the host cells. JHU researchers developed novel proteasome inhibitors that kill cells transformed with high-risk strains of HPV and restore expression of the tumor suppressor protein p53. The candidate compounds are able to induce apoptosis as single agents in a broad spectrum of HPV-transformed tumor cell lines. Description (Set) Proposed Use (Set) This invention provides lead compounds for the treatment of cervical cancer.

Inventor(s): Khan, Saeed R.

Type of Offer: Licensing

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