Overcoming the Limitations of Endocrine Therapy for Ovarian Cancer
Abstract
Epidemiological evidence suggests that steroid hormones may play a role in the pathogenesis of ovarian cancer. However, clinical trials utilizing endocrine therapies for the treatment of relapsed or recurrent ovarian cancer have largely failed to produce meaningful patient responses. Estrogen Receptor (ER) Alpha is a steroid hormone receptor that has been well characterized as a primary driver of both breast and endometrial cancers. However, despite the observation that the majority of high grade serous (HGSC) and endometrioid ovarian cancers express ER Alpha, the role of ER Alpha in ovarian cancer is not well understood. Our preliminary data have demonstrated that estradiol (E2) is sufficient to increase proliferation in the ER+ ovarian cancer cell line PEO1 and this increase in proliferation was attenuated by tamoxifen or fulvestrant. Furthermore, we found that E2 stimulates a transcriptome and cistrome in PEO1cells that is distinct from that of breast cancer cells. We have also determined that the AP-1 transcription factor, FOSL2, is required for ER transcriptional activity and epigenetic remodeling at ER binding sites in ovarian cancer cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2020
- Accession Number
- AD1114473
Entities
People
- Myles A. Brown
Organizations
- Dana–Farber Cancer Institute