Romidepsin for the treatment of cutaneous T-cell lymphoma

Abstract

Aberrant epigenetic gene regulation by deacetylation of histone proteins has been involved in tumorigenesis. Histone deacetilase (HDAC) inhibitors are promising anticancer agents under research and development. Romidepsin is a novel and potent HDAC inhibitor highly efficient in inhibiting HDAC activity even at nanomolar concentrations. It exhibits a considerably stronger direct inhibition in class I HDAC enzymes as compared to class II. In addition of histone deacetylation, romidepsin modulates additional targets involved in cancer initiation and progression such as c-myc, Hsp90 and p53. Romidepsin has shown promising anticancer effects in a wide variety of nonclinical cancer models both in vitro and in vivo by induction of apoptosis, cell differentiation and cell cycle arrest. Romidepsin has been recently approved by the FDA for the treatment of cutaneous T-cell lymphoma (CTCL) patients who have received at least one prior systemic therapy. It is currently under clinical investigation for the treatment of other hematological malignances and solid tumors as monotherapy and in combination with other anticancer agents.