A Novel Combination Treatment for Ovarian Granulosa Cell Tumors
Abstract
Ovarian granulosa cell tumors (GCT) are hormonally-active neoplasms characterized by endocrine manifestations, an indolent course and late recurrence. Treatment involves surgery, and chemo- or hormonal-therapy have limited efficacy. This proposal will address the development of a novel GCT specific therapeutic strategy. The survival transcription factor, NFkB, is activated in these tumors; inhibition of this pathway promotes apoptosis. Peroxisome proliferator-activated receptor-gamma protein (PPARgamma), a transcription factor that impedes growth and promotes differentiation, is overexpressed in GCT, but transrepressed by NFkB signaling in GCT. An NFkB-induced protein, X-linked inhibitor of apoptosis protein (XIAP), is also overexpressed in GCT and is critical in preventing GCT cell apoptosis and represents an attractive therapeutic target. We hypothesize that 1) PPARgamma and XIAP play fundamental roles in the regulation of granulosa cell (GC) apoptosis, and/or terminal differentiation, albeit in a reciprocal manner, and 2) that combined targeting of PPARgamma and XIAP presents a novel therapeutic strategy for GCT treatment.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2020
- Accession Number
- AD1130771
Entities
People
- Simon Chu
Organizations
- Hudson Institute of Medical Research