Inhibition of Noncanonical NF-kappaB for Treatment of Ovarian Cancer
Abstract
Inhibition of non-canonical NF-kappaB for treatment of ovarian cancer Background. Whether the non-canonical NF-kB signaling pathway (nc-NF-kB) represents a novel, distinct and improved target for therapy in ovarian cancer is unknown. In nc-NF-kB signaling, the p100/RelB complex in the cytoplasm, p100 is processed to truncated p52 and the complex translocates to the nucleus and mediates signaling. We have preliminary data showing that human and mouse ovarian cancer cells express nuclear p52, indicative of active nc-NF-kB signaling. Additional preliminary data shows inhibited growth of ovarian cancer cells via treatment with SN52 peptide that specifically inhibits nuclear import of p52 and RelB. Preliminary data also shows that mouse bone marrow-derived macrophages (BMDMs) polarized towards the M2 pro-tumor phenotype expresses higher levels of nuclear p52 than M1 or un-polarized cells. Moreover, high expression of p52 in high-grade serous ovarian tumors is associated with worse patient prognosis. This cumulative evidence suggests that nc-NF-kB represents an unrecognized therapeutic target.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2023
- Accession Number
- AD1209699
Entities
People
- Fiona E. Yull
Organizations
- Vanderbilt University