The Role of HDACS in T-Cell

The overall goal of this research endeavor is to discover and optimize epigenetic-based treatment strategies for the treatment of peripheral T-cell lymphoma (PTCL). PTCL is a rare and heterogeneous group of aggressive lymphomas, and historically represents one of the most difficult to treat forms of lymphoma. Much of this stems from the fact that these diseases have been poorly understood until recently, and the treatment platforms for these diseases has been largely derived from those for other unrelated lymphomas. Our group, under the direction of Dr. O’Connor, led the some of the first studies of an HDAC inhibitor in patients with lymphoma (formerly known as SAHA, now known as vorinostat), which eventually led to vorinostat becoming the first HDAC inhibitor approved for the treatment of any cancer. In fact, in November 2006, vorinostat was approved by the U.S. FDA for the treatment of patients with cutaneous T-Cell lymphoma. HDAC inhibitors are known to modify the acetylation of histone and non-histone proteins, and to modulate gene expression. More recently romidepsin has been approved by the U.S. FDA for the treatment of both PTCL and CTCL, firmly establishing that T-cell lymphomas are sensitive to these epigenetic drugs. Collectively, these data have clearly established that targeting T-cell lymphomas with epigenetic therapies, including HDAC inhibitors and hypomethylating agents, is an effective and safe, ‘chemotherapy-free’ strategy to manage these diseases.