Abstract
Epigenetic mechanisms play an important role in the development and persistence of cancer, and histone deacetylase (HDAC) inhibitors are promising anticancer drugs targeting epigenetic modes. Efficient anticancer drugs for the treatment of castration-resistant prostate cancer (CRPC) are sought, and approved HDAC inhibitors have shown promising results on the one hand and severe drawbacks on the other hand. Hence, ways to break the drug resistance mechanisms of existing HDAC inhibitors as well as the design of new promising HDAC inhibitors which can overcome the disadvantages of the classic HDAC inhibitors are of great importance. In this work, HDAC inhibitors with the potential to become a mainstay for the treatment of CRPC in the future as well as suitable combination treatments of HDAC inhibitors with other anticancer drugs leading to considerable synergistic effects in treated CRPCs are discussed.
Highlights
More than 1.2 million new cases of prostate cancer cases are reported per year worldwide (2018) rendering prostate cancer the second most diagnosed cancer in men along with a rising incidence over the last years[1]
Clinical trials have shown that monotherapy with histone deacetylase (HDAC) inhibitors cannot be recommended for phase 3 studies due to low efficacy and considerable toxicity in castration-resistant prostate cancer (CRPC) patients
DNA methylation inhibitors, PARP inhibitors, various protein kinase and mTOR inhibitors, interferon, and TRAIL gene therapy appeared to be suitable combination partners for HDAC inhibitors, which should be considered for future clinical studies with CRPC patients
Summary
More than 1.2 million new cases of prostate cancer cases are reported per year worldwide (2018) rendering prostate cancer the second most diagnosed cancer in men along with a rising incidence over the last years[1]. Inhibition of DNA methylation was positively correlated with HDAC inhibition and sodium butyrate in combination with the DNA methyltransferase inhibitor 5-aza-2’-deoxycytidine significantly enhanced histone H4 acetylation and induced AR gene reexpression in androgen-independent DU145 prostate cancer cells.
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