Histone Deacetylase Inhibitors for Peripheral T-Cell Lymphomas

Simple Summary Nodal peripheral T-cell lymphomas (PTCLs) are among the most aggressive lymphomas and in the majority of cases are considered incurable. Therefore, there is a cogent need for novel therapies. In this review, the authors analyzed the biological rationale, the experimental experience, and the real-world data concerning the use of histone deacetylase inhibitors (HDACis) to treat PTCLs.Abstract Histone deacetylase inhibitors (HDACis) are being recognized as a potentially effective treatment approach for peripheral T-cell lymphomas (PTCLs), a heterogeneous group of aggressive malignancies with an unfavorable prognosis. Recent evidence has shown that HDACis are effective in treating PTCL, especially in cases where the disease has relapsed or is resistant to conventional treatments. Several clinical trials have demonstrated that HDACis, such as romidepsin and belinostat, can elicit long-lasting positive outcomes in individuals with PTCLs, either when used alone or in conjunction with conventional chemotherapy. They exert their anti-tumor effects by regulating gene expression through the inhibition of histone deacetylases, which leads to cell cycle arrest, induction of programmed cell death, and,the transformation of cancerous T cells, as demonstrated by gene expression profile studies. Importantly, besides clinical trials, real-world evidence indicated that the utilization of HDACis presents a significant and beneficial treatment choice for PTCLs. However, although HDACis showed potential effectiveness, they could not cure most patients. Therefore, new combinations with conventional drugs as well as new targeted agents are under investigation.