A New Paradigm for the Treatment of Ovarian Cancer: The Use of Epigenetic Therapy to Sensitize Patients to Immunotherapy and Chemotherapy
Abstract
The overall goal of this project remains to bring epigenetic therapy strategies to have major impact for the management of advanced ovarian cancer (OC). This past year, we continue to make exciting advances and all of our pre-clinical work is about to impact a leveraged clinical trial now ready to start wherein low dose therapy targeting DNA demethylation will be paired with immune checkpoint therapy. Our latest studies of a mouse model of serous ovarian cancer has progressed significantly in which we have identified the demethylating agent, 5-aza-cytidine (AZA) potently stimulates tumor immune attraction of T-cells to the tumor microenvironment. This augmented by addition of a histone deactylase inhibitor (HDACi) in a newly derived regimen and addition of the immune checkpoint therapy, anti-PD1 adds to tumor inhibition and prolongs survival of the mice. We are now working to determine whether an AZA induced interferon triggering pathway involving upregulation of a cytosolic double stranded RNA(dsRNA) sensing system and of endogenous retroviral transcripts (ERVs), published last year, is the mechanism triggering the above immune response.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2016
- Accession Number
- AD1035730
Entities
People
- Stephen B. Baylin
Organizations
- Johns Hopkins University