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Romidepsin for the treatment of non-Hodgkin's lymphoma
Victor Y Yazbeck1, Steven Grant
1Virginia Commonwealth University, Massey Cancer Center , Richmond, VA , USA.
Introduction:
Patients with relapsed or refractory lymphoma remain a population with unmet medical needs. Histone deacetylase inhibitors (HDACIs) represent a novel class of anticancer drugs currently in development in several malignancies. Inhibition of HDACs leads to acetylation of histone and non-histone proteins, which in turn results in epigenetic modification of gene expression that leads to a plethora of effects, such as cell cycle arrest, apoptosis and inhibition of angiogenesis. Romidepsin is a novel HDACI that has demonstrated preclinical and clinical activity.
Areas Covered:
This review discusses the different HDACs and epigenetic regulation with a particular focus on the preclinical and clinical development of romidepsin in lymphoma. The review of romidepsin includes: the mechanism of action, its synergistic interaction with novel agents, pivotal clinical trials that lead to its US FDA approval in cutaneous T-cell lymphoma and peripheral T-cell lymphoma as well as active combinations currently in clinical trials.
Expert Opinion:
Romidepsin is a potent HDACI with clinical activity in T-cell lymphoma where novel agents and combinations are desperately needed. A deeper understanding of the molecular characteristics of this class of agents will allow the design of more potent drugs with improved toxicity profiles and future rational combinations that will expand the indication and benefit from these novel agents.
Insights
Romidepsin, a histone deacetylase inhibitor (HDACI), shows promise for treating T-cell lymphoma. Further research into its molecular characteristics will guide the development of more effective treatments and combinations for patients with unmet medical needs.
Area of Science:
- Oncology
- Epigenetics
- Pharmacology
Background:
- Relapsed or refractory lymphoma presents significant unmet medical needs.
- Histone deacetylase inhibitors (HDACIs) are a novel class of anticancer drugs impacting gene expression through epigenetic modification.
- Romidepsin is an HDACI with demonstrated preclinical and clinical activity.
Purpose of the Study:
- To review the preclinical and clinical development of romidepsin in lymphoma.
- To discuss the mechanism of action and synergistic interactions of romidepsin.
- To highlight pivotal clinical trials and ongoing combinations involving romidepsin.
Main Methods:
- Review of scientific literature on HDACs and epigenetic regulation.
- Analysis of romidepsin's mechanism of action and preclinical data.
- Examination of clinical trial outcomes and ongoing research for romidepsin in lymphoma.
Main Results:
- Romidepsin exhibits clinical activity in T-cell lymphomas.
- HDACIs induce effects such as cell cycle arrest, apoptosis, and inhibition of angiogenesis.
- Romidepsin received US FDA approval for cutaneous T-cell lymphoma and peripheral T-cell lymphoma.
Conclusions:
- Romidepsin is a potent HDACI with significant clinical activity in T-cell lymphoma.
- There is a critical need for novel agents and combination therapies for T-cell lymphoma.
- Understanding romidepsin's molecular properties will enable the design of improved drugs and rational combinations for expanded therapeutic benefit.
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