UNMET NEED
Cancers are now recognized as being driven by widespread changes in the epigenome including changes in DNA methylation and chromatin packaging. Changes in DNA methylation include global loss of methylation and focal gain of methylation at promoter regions of tumor suppressor genes leading to transcriptional silencing. DNA methylation, the covalent modification of DNA, is mediated by a family of DNA methyltransferases (DNMTs). In recent years, inhibitors of DNMTs (DNMTis) have emerged as therapeutic targets for treatment of myeloid malignancies as well as cutaneous T cell lymphoma. In 2004, the FDA approved the DNMT inhibitor 5-azacitidine (AZA) for treatment of myelodysplastic syndrome. However, new and better therapies for treating cancer are desperately needed.
PROBLEM SOLVED
Johns Hopkins researchers have discovered that solid tumors can be treated with a combination therapy of a demethylatingagent, an HDAC inhibitor and a checkpoint inhibitor. They found that:
1. mice treated with 5-Azacytidine (AZA) combined with anti-PD-1 and with HDAC inhibitors survived longer than untreated mice or mice given a single agent.
2. mice treated with AZA combined with HDAC inhibitors survived longer than untreated mice or mice given a single agent.
3. mice treated with 5-Azacytidine (AZA) combined with anti-PD-1 and HDAC inhibitors developed less ascites fluid than untreated or mice given a single agent.
STAGE OF DEVELOPMENT
Preclinical data obtained in Human Breast, Ovarian and Colorectal cancer samples.
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