Epigenetic approaches to prostate cancer: Present landscape and future prospects
Konstantinos Mesiakaris1, Efthalia Kontogianni1, Susan Logotheti1
1Department of Pathology, School of Medicine, University of Patras, Greece.
Abstract:
Genetic profiles alone do not fully describe the development and evolution of prostate cancer (PCa), whereas epigenetic alterations are emerging as promising therapeutic targets. This review explores FDA-approved and experimental epigenetic strategies, including DNA methyltransferase inhibitors (DNMTis), histone deacetylase inhibitors (HDACis), histone methyltransferase inhibitors, bromodomain and extra-terminal domain inhibitors (BETi), non-coding RNA therapies, antisense oligonucleotides, and future prospects such as chromatin remodeling, DNA hydroxymethylation, and RNA methylation. Although DNMTis and HDACis have historically dominated clinical trials, mainly in hematologic cancers, the 2020 approval of an epigenetic therapy for a solid tumor marked an important breakthrough. Despite this, epigenetic drugs remain underexplored in PCa: among 2254 clinical studies of such agents, only 58 (2.57 %) included PCa patients. This disparity highlights an urgent need for novel therapeutic approaches beyond chemotherapy and androgen deprivation. By assessing current progress and outlining opportunities in drug repositioning and novel targets, this review underscores epigenetics as a critical frontier for advancing PCa treatment.
Insights
Epigenetic alterations are key to prostate cancer (PCa) evolution and treatment. This review highlights underutilized epigenetic drugs and future targets for PCa therapy, emphasizing their potential beyond traditional treatments.
Area of Science:
- Oncology
- Epigenetics
- Cancer Therapeutics
Background:
- Prostate cancer (PCa) development and evolution are not fully explained by genetics alone.
- Epigenetic alterations are increasingly recognized as crucial therapeutic targets in cancer.
- Current PCa treatments like chemotherapy and androgen deprivation have limitations.
Purpose of the Study:
- To review FDA-approved and experimental epigenetic strategies for cancer treatment.
- To assess the current status and future prospects of epigenetic therapies in prostate cancer.
- To highlight the underrepresentation of PCa in clinical trials for epigenetic drugs.
Main Methods:
- Review of FDA-approved and experimental epigenetic agents.
- Analysis of clinical trial data for epigenetic therapies, focusing on PCa inclusion.
- Exploration of emerging epigenetic targets and strategies.
Main Results:
- Epigenetic drugs, including DNA methyltransferase inhibitors (DNMTis) and histone deacetylase inhibitors (HDACis), show promise.
- A 2020 approval marked a breakthrough for epigenetic therapy in solid tumors.
- Only 2.57% of epigenetic drug clinical studies include PCa patients, indicating significant underutilization.
Conclusions:
- Epigenetic therapies represent a critical, underexplored frontier for advancing prostate cancer treatment.
- There is an urgent need for novel therapeutic approaches targeting epigenetic modifications in PCa.
- Drug repositioning and novel epigenetic targets offer significant opportunities for improving PCa outcomes.
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