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Updated: May 27, 2026
Assays for Validating Histone Acetyltransferase Inhibitors
Published on: August 6, 2020
Finding the place of histone deacetylase inhibitors in prostate cancer therapy
Deborah L Marrocco-Tallarigo1, Margaret M Centenera, Howard I Scher
1Dame Roma Mitchell Cancer Research Laboratories, School of Medicine, University of Adelaide and Hanson Institute, Adelaide, SA 5000, Australia. deborah.marrocco@adelaide.edu.au.
Abstract:
Histone deacetylase inhibitors (HDACIs) are showing promise as therapeutic agents for hematological malignancies and solid tumors. In the case of prostate cancer, HDACIs are effective at inhibiting proliferation and inducing apoptosis in a range of in vitro and in vivo experimental models. Recent studies have revealed that the actions of HDACIs in prostate cancer cells extend beyond regulation of histone acetylation and affect proteins involved in maintaining cellular homeostasis and tumor progression, including the androgen receptor, p21(WAF1) and VEGF. The broad spectrum of HDACI targets has allowed rational design of combinations with other therapeutic agents to target multiple pathways involved in prostate cancer progression, including angiogenesis and androgen signaling. In particular, synergistic inhibition of prostate cancer cell growth has been demonstrated using HDACIs in combination with radio- and chemo-therapy, Apo2L/TRAIL, angiogenesis inhibitors, heat-shock protein 90 inhibitors and androgen receptor antagonists. This review examines the current understanding of the actions of HDACIs in prostate cancer cells, both in a laboratory and a clinical context and discusses the potential utility of combination strategies for the treatment of prostate cancer.
Insights
Histone deacetylase inhibitors (HDACIs) show promise for treating prostate cancer by inhibiting cell growth and survival. Combining HDACIs with other therapies may enhance treatment efficacy for this malignancy.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Histone deacetylase inhibitors (HDACIs) are emerging as potent therapeutic agents for various cancers, including hematological malignancies and solid tumors.
- In prostate cancer models, HDACIs effectively inhibit cell proliferation and induce apoptosis.
- Emerging research indicates that HDACIs influence key cellular pathways beyond histone acetylation, impacting proteins like the androgen receptor, p21(WAF1), and VEGF, which are critical for cellular homeostasis and tumor progression.
Purpose of the Study:
- To review the current understanding of histone deacetylase inhibitor (HDACI) actions in prostate cancer cells.
- To explore the potential of combination strategies involving HDACIs for prostate cancer treatment.
Main Methods:
- Review of in vitro and in vivo experimental models of prostate cancer treated with HDACIs.
- Analysis of studies investigating the molecular targets of HDACIs in prostate cancer cells.
- Examination of clinical data and preclinical studies on combination therapies involving HDACIs.
Main Results:
- HDACIs demonstrate efficacy in inhibiting prostate cancer cell proliferation and inducing apoptosis.
- HDACIs modulate critical proteins such as the androgen receptor, p21(WAF1), and VEGF, affecting cellular homeostasis and tumor progression.
- Combinations of HDACIs with radio-/chemotherapy, Apo2L/TRAIL, angiogenesis inhibitors, HSP90 inhibitors, and androgen receptor antagonists show synergistic inhibition of prostate cancer cell growth.
Conclusions:
- HDACIs represent a promising therapeutic strategy for prostate cancer, acting through diverse molecular mechanisms.
- Combination therapies involving HDACIs offer a rational approach to target multiple pathways crucial for prostate cancer progression, potentially improving treatment outcomes.
