Researchers at the University of California, Davis have developed methods for creating compositions with the potential to prevent or treat cancer or metabolic diseases. These compositions combine conjugates with covalently linked HDAC inhibitors and retinoids.
Despite steady therapy advances, cancer remains a prominent global disease. Furthermore, metabolic diseases such as diabetes, obesity, non-alcoholic steatohepatitis (NASH) and non-alcoholic fatty liver disease (NAFLD) also pose prominent threats to health worldwide. Thus, there is a need for new treatments for both cancer and various metabolic diseases. Previous research has shown that the combination of histone deacetylase (HDAC) inhibitors and retinoids can be effective treatments for cancer and metabolic diseases. However, synthetic HDAC inhibitors such as suberanilohydroxamic acid (SAHA) have toxicity concerns, and natural gut bacteria-generated HDAC inhibitors such as butyrate have low bioavailability due to their rapid metabolism and clearance.
Researchers at the University of California, Davis have developed compositions comprising conjugates with a polymeric backbone and covalently linked HDAC inhibitors and retinoids. These compositions have documented benefits in the treatment or prevention of cancer or metabolic diseases, particularly in colon and liver tissue. In contrast to the therapeutic shortcomings of individual drugs such as butyrate and retinoic acid (RA), the conjugates developed assemble into nanomicelles and release HDAC inhibitors and retinoids through slow hydrolysis, resulting in long-lasting efficacy. Moreover, the conjugates are orally deliverable, which is preferred by patients and much more cost-effective in low-resource settings (oral administration saves dispending and administration costs). The present formulations are effective in both the colon and the liver, and thus can be used for both colon and liver cancer, as well as metabolic disease associated with both organs.
HDACi, HDAC, retinoids, NASH, NAFLD, conjugate, cancer, liver, colon