Chimeric HDAC inhibitors as a novel therapeutic approach for prostate cancer
Histones are small basic proteins located in the cell nucleus of eukaryotes. They play a crucial role in the organization of cellular DNA. The primary function of histones is to package DNA in a way that allows it to fit into the cell nucleus. At the same time, it must be ensured that essential DNA functions such as transcription and replication can proceed in a regulated manner. Transcriptional regulation is achieved, among other mechanisms, through acetylation and deacetylation of chromatin mediated by histone acetyltransferases and histone deacetylases (HDACs).
The inhibition of HDACs using specific inhibitors represents a promising strategy for the pharmacological treatment of prostate cancer, as prostate carcinoma exhibits tumor-specific alterations in HDAC expression that can be exploited as targets for targeted cancer therapy.
In Ms. Groth’s research project, HDAC inhibitors with dual or multimodal mechanisms of action are being investigated for their antitumor and antiangiogenic effects in prostate cancer. The so-called chimeric HDAC inhibitors used in this project combine histone deacetylase–inhibiting properties with additional tumor cell–damaging effects, such as cytoskeletal disruption or tyrosine kinase inhibition, within a single molecule. The resulting simultaneous targeting of multiple vital signaling pathways and tumor blood supply (tumor angiogenesis) is characterized at the cellular, molecular, and systemic levels, and the antineoplastic potential of these novel chimeric HDAC inhibitors is compared with clinically relevant therapeutic agents and combination treatment strategies.
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