A New Paradigm for the Treatment of Ovarian Cancer: The Use of Epigenetic Therapy to Sensitize Patients to Immunotherapy and Chemotherapy
Technical Report,30 Sep 2016,29 Sep 2017
Johns Hopkins University Baltimore United States
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Our overall goal remains to bring epigenetic therapy to have major impact for the management of advanced ovarian cancer OC. This past year, we continue to make exciting advances in our pre-clinical work and are now enrolling a leveraged clinical trial for low dose therapy targeting DNA demethylation paired with immune checkpoint therapy. Moreover, we have now completed two studies of mouse models. First, is an in press PNAS study of a serous ovarian cancer in which we have identified that the demethylating agent, 5-aza-cytidine AZA potently stimulates tumor immune attraction of T-cells to the tumor microenvironment. The treatment paradigm involves a newly regimen we first derived for addition of a histone deactylase inhibitor HDACi in a study of mouse models for lung cancer and this work is also now in press for Cell. In all the above, we document that an AZA induced interferon triggering pathway that we published in Cell in 2015 is a key mechanism triggering the above immune responses. Moreover in the upcoming Cell paper, we also show a key role for down-regulating the CMYC oncogene signaling for the epigenetic therapy to reverse tumor immune evasion and attract activated T-cells.
- Medicine and Medical Research