Largazole as a Novel and Selective Anti-Breast Cancer Agent

Breast cancer is the second most common type of cancer in the world and second most common cause of deaths in US. There is great a demand for new, small molecule, drugs that can selectively eliminate breast cancer cells. Many natural compounds have anti-tumor activities e.g. Taxol . Recently we achieved a total synthesis of Largazole and demonstrated that this natural compound has remarkable selectivity toward breast cancer cells. We also find that Largazole can block two cellular activities frequently associated with aggressive tumor cells. In this proposal, we will test whether dual inhibition of two oncogenic pathways may be the reason why Largazole is highly selective against tumor cells but not normal cells. We will develop more potent and selective small molecules to validate the concept that dual specificity inhibitors are better anti-cancer drugs. Our studies are expected to provide novel ideas for designing more effective therapeutics for breast cancer treatment.