Mechanism of Action: DNA methyltransferase (DNMT) inhibition
Indication: Solid tumors
How this therapy can help
As a next generation DNA-hypomethylating agent that targets and reverses aberrant DNA hypermethylation, an epigenetic change characteristic of many cancer cells, it restores the expression of silenced tumor suppressor genes and cancer testis antigens. Guadecitabine-mediated demethylation of DNA upregulates tumor-associated antigens, and may sensitize tumor cells to other anticancer agents, including immunotherapeutics, as well as resensitizing resistant cancer cells to chemotherapeutics. Guadecitabine was rationally designed to prolong the exposure of tumor cells to the active moiety, decitabine, ensuring greater uptake of decitabine into the DNA of rapidly dividing cancer cells.
Guadecitabine is being tested in clinical trials for the treatment of solid tumors, including studies investigating combination with carboplatin in the treatment of platinum-resistant ovarian cancer, in hepatocellular (liver) cancer following failure of Nexavar (sorafenib), and in combination with irinotecan in the treatment of colorectal cancer.