Metastasis—the leading cause of cancer death—occurs when so-called disseminated cancer cells (DCCs) escape from primary tumors and travel through the bloodstream to other organs, where—sometimes after remaining dormant for decades—they reactivate. In 2015, Julio Aguirre-Ghiso, Ph.D., and colleagues published evidence that the combination of two U.S. Food and Drug Administration-approved drugs—5-azacytidine (AZA) and retinoic acid (atRA)—can restore gene programs that suppress the growth of malignant cancer cells. Those results led the V Foundation for Cancer Research to fund a clinical trial to evaluate whether the drug combination can prevent or delay metastasis progression in prostate cancer patients; Dr. Aguirre-Ghiso was the principal investigator on the V Foundation grant, which also explored how AZA and atRA could block metastasis.  

In a paper published online on June 1 in Cell Reports, Dr. Aguirre-Ghiso’s team found that the drug combination suppresses metastasis in oral carcinoma animal models. DCCs that become metastatic were found to deactivate TGFb-SMAD4 signaling, which maintains DCCs in a dormant state; combining AZA with atRA epigenetically reprogrammed the DCCs, restoring TGFb-SMAD4 signaling and preventing DCCs from reactivating. By inducing DCC dormancy, the AZA and atRA combination may represent a new therapy for preventing or delaying metastatic disease.

Dr. Aguirre-Ghiso is the Rose C. Falkenstein Chair in Cancer Research, professor of cell biology, of medicine, and of oncology, director of the Cancer Dormancy and Tumor Microenvironment Institute at Montefiore Einstein Cancer Center, and co-director of the Gruss-Lipper Biophotonics Center at Einstein.