Clinical efficacy and mechanistic insights of FDA-approved HDAC inhibitors in the treatment of lymphoma

Lymphomas are complex malignancies of blood cells, characterized by the malignant transformation of lymphocytes. This transformation is partially driven by disruptions in epigenetic regulation, particularly the acetylation of histones. Among the key players in this process are histone deacetylases (HDACs), whose aberrant activity contributes significantly to lymphoma development. Consequently, targeting HDACs represents a promising pharmacotherapeutic approach. Several HDAC inhibitors (HDACis) have demonstrated significant anticancer effects, with four FDA-approved molecules—vorinostat, romidepsin, belinostat, and panobinostat—forming critical components of chemotherapy regimens for lymphoma treatment. These HDAC inhibitors exhibit their therapeutic efficacy through mechanisms that indirectly impact cellular memory and induce cancer cell death via apoptosis and cell cycle arrest. Their clinical effectiveness is particularly notable in various types of lymphomas, underscoring their therapeutic potential. The objective of this review is to provide a detailed analysis of FDA-approved HDACis, focusing on their molecular mechanisms of action and clinical applications in lymphoma treatment. Specifically, we aim to elucidate how these inhibitors modulate epigenetic regulation to achieve therapeutic efficacy, highlight their utility across different lymphoma subtypes, and examine their integration into combination therapies with other anticancer agents. Furthermore, this review seeks to identify gaps in current knowledge and propose directions for future research, including the development of next-generation HDAC inhibitors and strategies for optimizing their clinical use. By consolidating existing evidence, we strive to enhance the understanding of HDACis' role in lymphoma therapy and inspire advancements in their therapeutic potential.