Integration of class 1 HDAC inhibitors into current treatments for prostate cancer
type: CreativeWork
description: Introduction: Prostate Cancer (CaP) is the most common non-cutaneous malignancy in men in the Western world and therefore a significant health burden worldwide. First-line standard-of-care therapies for organ confined, locally advanced prostate cancer (LAPC) are surgery and radiotherapy. Although highly effective, relapse to recurrent disease occurs in 20-50% of men and resistance to subsequent hormonal therapies results in progression to incurable castrate resistant prostate cancer (CRPC). Androgen signalling inhibitors (ASI), including Enzalutamide (ENZ) and Abiraterone (ABI), are effective treatments for metastatic CRPC however, resistance develops within 24-months of initial exposure in the majority of patients. Epigenetic silencing of cancer-related genes has been shown to be highly influential in CaP disease development and progression and epigenetic regulators, including histone deacetylases (HDAC), are commonly mutated and highly expressed in cancer, representing attractive clinical targets. Although five HDAC inhibitors (HDACi) have been FDA approved for myelodysplastic syndromes, evaluation of pan-HDACi in CaP clinical trials as single agents have been ineffective to date largely due to treatment-related toxicity and efficacy as monotherapies. To be able to incorporate HDACi into the treatment of CaP, the reduction of toxicity must be addressed including the use of a more specific targeted approach such as class specific HDACi. Class 1 HDAC isozymes are highly expressed in CaP and the Class 1 specific HDACi Entinostat (ENT) has been awarded FDA designation as a breakthrough therapy for aromatase inhibitor (AI)-resistant breast cancer in combination with hormone therapy demonstrating its potential to be used for treatment of solid tumours including CaP. In addition, the identification of an appropriate combination partner with HDACi and optimal scheduling of treatment will be beneficial in improving response to treatment and lowering the required dose, ther…
abstract: Introduction: Prostate Cancer (CaP) is the most common non-cutaneous malignancy in men in the Western world and therefore a significant health burden worldwide. First-line standard-of-care therapies for organ confined, locally advanced prostate cancer (LAPC) are surgery and radiotherapy. Although highly effective, relapse to recurrent disease occurs in 20-50% of men and resistance to subsequent hormonal therapies results in progression to incurable castrate resistant prostate cancer (CRPC). Androgen signalling inhibitors (ASI), including Enzalutamide (ENZ) and Abiraterone (ABI), are effective treatments for metastatic CRPC however, resistance develops within 24-months of initial exposure in the majority of patients. Epigenetic silencing of cancer-related genes has been shown to be highly influential in CaP disease development and progression and epigenetic regulators, including histone deacetylases (HDAC), are commonly mutated and highly expressed in cancer, representing attractive clinical targets. Although five HDAC inhibitors (HDACi) have been FDA approved for myelodysplastic syndromes, evaluation of pan-HDACi in CaP clinical trials as single agents have been ineffective to date largely due to treatment-related toxicity and efficacy as monotherapies. To be able to incorporate HDACi into the treatment of CaP, the reduction of toxicity must be addressed including the use of a more specific targeted approach such as class specific HDACi. Class 1 HDAC isozymes are highly expressed in CaP and the Class 1 specific HDACi Entinostat (ENT) has been awarded FDA designation as a breakthrough therapy for aromatase inhibitor (AI)-resistant breast cancer in combination with hormone therapy demonstrating its potential to be used for treatment of solid tumours including CaP. In addition, the identification of an appropriate combination partner with HDACi and optimal scheduling of treatment will be beneficial in improving response to treatment and lowering the required dose, ther…
author: Manley, Judith
language: eng
date published: 2020-12
date modified: 2026-07-24T03:55:31Z
provider: Queen's University Belfast
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Queen's University Belfast