Role of Histone Deacetylase (HDAC) Inhibitors for the Treatment of Cutaneous T-Cell Lymphoma (CTCL)

Abstract

HDACs regulate variety of cell functions. Several structurally distinct classes of HDAC inhibitor have been developed. Cutaneous T-cell lymphoma(CTCL) is a clinically and immunologically defined neoplasm which encompasses epidermotropic (mycosis fungoides, Sezary syndrome) and non-epidermotrepic variants. CTCL lymphoma comprises a heterogenous group of lymph proliferative disorders, characterised by clonal expansions of mature post thymic T-cells that infiltrate the skin. The USFDA have been approved many HDAC inhibitors such as Vorinostat, Romidepsin, Belinostat, Panobinostat in which the Vorinostat and Romidepsin has been approved for treatment of CTCL. The response rate shown in Histone deacetylase inhibitor in CTCL for Romidepsin was 34%-35%. Whereas the result of overall response rate of Vorinostat is 24%-30% in refractory advanced patients with CTCL. The impact on cell survival signalling varied with molecular phenotype this study suggests that cellular response to HDACs can be viewed as two distinct effect chromatin effect and a cell death effect. The divergent apoptotic responses observed reflect the variable clinical outcome of HDACi treatment. Romidepsin is potent inhibitors offers a promising new treatment for a disease with few existing therapies. We also found Romidepsin to be a more effective than Vorinostat. Our further objective was to further study the clinical benefits of Romidepsin in patients that had the best response of Stable Disease (SD).