Romidepsin (Histone Deacetylase Inhibitor)

Proposed Mechanism of Action

The epigenetic modifier romidepsin is a potent class 1 selective histone deacetylase inhibitor.1-2 Altered expression, dysregulation, and mutations of histone deacetylase (HDAC) genes have been implicated in tumor development in cells of various cancers.3,4 In preclinical studies, HDAC inhibitors, such as romidepsin, prevent HDACs from removing acetyl groups, both allowing DNA to remain transcriptionally active (eg, tumor suppressor genes) and maintaining the acetylation of non-histone proteins (eg, genes involved in cell growth and differentiation).1,3,5 The downstream anti-cancer effects of HDAC inhibitors potentially include interference with cell cycle and mitosis, decreased cell motility, decreased angiogenesis, cell differentiation, and cell death.1,3,4,6

HAT, histone acetyltransferase; HDAC, histone deacetylase.

Romidepsin by Disease State

Romidepsin in Lymphoma

  • Post Approval Research Lymphoma Cutaneous T-cell lymphoma (US)
  • Post Approval Research Lymphoma Peripheral T-cell lymphoma: Relapsed/refractory
  • Phase 3 Lymphoma Peripheral T-cell lymphoma: First-line

Preclinical work showing anti-tumor properties of romidepsin provides support for clinical studies of this compound. Romidepsin is being investigated in a phase III study in combination with chemotherapy vs chemotherapy alone in patients with previously untreated PTCL.

The safety and efficacy of the agents and/or uses under investigation have not been established. There is no guarantee that the agents will receive health authority approval or become commercially available in any country for the uses being investigated

References

  1. Bolden JE, et al. Nat Rev Drug Discov. 2006;5:769-784.
  2. Bradner JE, et al. Nat Chem Biol. 2010;6:238-243.
  3. New M, et al. Mol Oncol. 2012;6:637-656.
  4. Marsoni S, et al. Epigenetics. 2008;3:164-171.
  5. Ho E, et al. J Nutr. 2009;139:2393-2396.
  6. Khan O, La Thangue NB. Immunol Cell Biol. 2012;90:85-94.