scholarly journals Castration-Resistant Prostate Cancer: Mechanisms, Targets, and Treatment

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Teresa Maria Santos Amaral ◽  
Daniela Macedo ◽  
Isabel Fernandes ◽  
Luis Costa
Keyword(s):  
Prostate Cancer ◽  
Clinical Trials ◽  
New Drugs ◽  
Rational Approach ◽  
Cancer Resistance ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Great Investment ◽  
New Treatments ◽  
Chemotherapy Agents

Patients with castration-resistant prostate cancer (CRPC), who progress after docetaxel therapy, had until very recently, only a few therapeutic options. Recent advances in this field brought about new perspectives in the treatment of this disease. Molecular, basic, and translational research has given us a better understanding on the mechanisms of CRPC. This great investment has turned into a more rational approach to the development of new drugs. Some of the new treatments are already available to our patients outside clinical trials and may include inhibitors of androgen biosynthesis; new chemotherapy agents; bone-targeted therapy; and immunotherapy. This paper aims to review the mechanisms of prostate cancer resistance, possible therapeutic targets, as well as new options to treat CRPC.

Optimal Sequencing of New Drugs in Metastatic Castration-Resistant Prostate Cancer: Dream or Reality?

2016 ◽  
Vol 17 (11) ◽  
pp. 1301-1308 ◽  
Author(s):  
Orazio Caffo ◽  
Andrea Lunardi ◽  
Chiara Trentin ◽  
Francesca Maines ◽  
Antonello Veccia ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
New Drugs ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Optimal Sequencing

scholarly journals Development of an Androgen Receptor Inhibitor Targeting the N-Terminal Domain of Androgen Receptor for Treatment of Castration Resistant Prostate Cancer

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3488
Author(s):  
Fuqiang Ban ◽  
Eric Leblanc ◽  
Ayse Derya Cavga ◽  
Chia-Chi Flora Huang ◽  
Mark R. Flory ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Splice Variants ◽  
Full Length ◽  
Cancer Resistance ◽  
Castration Resistant Prostate Cancer ◽  
Terminal Domain ◽  
Castration Resistant ◽  
Coregulatory Proteins ◽  
Androgen Binding

Prostate cancer patients undergoing androgen deprivation therapy almost invariably develop castration-resistant prostate cancer. Resistance can occur when mutations in the androgen receptor (AR) render anti-androgen drugs ineffective or through the expression of constitutively active splice variants lacking the androgen binding domain entirely (e.g., ARV7). In this study, we are reporting the discovery of a novel AR-NTD covalent inhibitor 1-chloro-3-[(5-([(2S)-3-chloro-2-hydroxypropyl]amino)naphthalen-1-yl)amino]propan-2-ol (VPC-220010) targeting the AR-N-terminal Domain (AR-NTD). VPC-220010 inhibits AR-mediated transcription of full length and truncated variant ARV7, downregulates AR response genes, and selectively reduces the growth of both full-length AR- and truncated AR-dependent prostate cancer cell lines. We show that VPC-220010 disrupts interactions between AR and known coactivators and coregulatory proteins, such as CHD4, FOXA1, ZMIZ1, and several SWI/SNF complex proteins. Taken together, our data suggest that VPC-220010 is a promising small molecule that can be further optimized into effective AR-NTD inhibitor for the treatment of CRPC.

Treatment Given Near the End of Life in Castration-Resistant Prostate Cancer

2012 ◽  
Vol 29 (7) ◽  
pp. 536-540 ◽  
Author(s):  
Hanna A. Zaghloul ◽  
Jose R. Murillo
Keyword(s):  
Quality Of Life ◽  
Prostate Cancer ◽  
End Of Life ◽  
Treatment Options ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Related Quality ◽  
Impact On Survival ◽  
New Treatments

Chemotherapy treatment options are limited for patients with castration-resistant prostate cancer (CRPC). The purpose of this study is to report treatment use and adverse effects (AEs) within the last three months of life in patients with CRPC. Of the 88 patients identified, 32% received treatment within 3 months of death, and documented AEs occurred in 25% of patients. Of those, neutropenia (18.3%), nausea/vomiting (18.3%), and febrile neutropenia (13.6%) were the most frequent. Results of this study show high treatment utility towards the end-of-life in patients with CRPC, with one fourth of patients experiencing AEs. Attention to health-related quality of life becomes increasingly important as new treatments appear to have small impact on survival, and AEs of those treatments may significantly impact patient quality of life.

scholarly journals Overview of the Development and Use of Akt Inhibitors in Prostate Cancer

2021 ◽  
Vol 11 (1) ◽  
pp. 160
Author(s):  
Anis Gasmi ◽  
Guilhem Roubaud ◽  
Charles Dariane ◽  
Eric Barret ◽  
Jean-Baptiste Beauval ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trials ◽  
Phase Ii ◽  
Critical Role ◽  
Castration Resistant Prostate Cancer ◽  
Loss Of Function ◽  
Pten Loss ◽  
Castration Resistant ◽  
Recent Phase ◽  
Phase Ii And Iii

Deregulation of the PI3K-Akt-mTOR pathway plays a critical role in the development and progression of many cancers. In prostate cancer, evidence suggests that it is mainly driven by PTEN loss of function. For many years, the development of selective Akt inhibitors has been challenging. In recent phase II and III clinical trials, Ipatasertib and Capivasertib associated with androgen deprivation therapies showed promising outcomes in patients with metastatic castration-resistant prostate cancer and PTEN-loss. Ongoing trials are currently assessing several Akt inhibitors in prostate cancer with different combinations, at different stages of the disease.

Novel therapies and emerging strategies for the treatment of patients with castration-resistant prostate cancer

2017 ◽  
Author(s):  
Deborah Mukherji ◽  
Aurelius Omlin ◽  
Carmel Pezaro ◽  
Johann De Bono
Keyword(s):  
Prostate Cancer ◽  
Abiraterone Acetate ◽  
Phase Iii ◽  
Trial Participation ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Radium 223 ◽  
New Treatments ◽  
Phase Iii Studies ◽  
Clinical And Translational Research

Castration-resistant prostate cancer (CRPC) represents a final stage of this malignancy for many men and is defined as the progression of prostate cancer despite castrate levels of testosterone. CRPC may present as a rising PSA, the development of new metastases, or worsening of known metastases. Recent advances have resulted in five new treatments for CRPC: the immunotherapy sipuleucel-T; the cytotoxic cabazitaxel; the androgen biosynthesis inhibitor abiraterone acetate; the radioisotope radium-223; and the antiandrogen enzalutamide. These have all improved overall survival in randomized phase III studies for patients with metastatic CRPC. Furthermore, multiple agents and combinations are currently in late-stage clinical testing. Men with advanced prostate cancer represent an important population for clinical and translational research and clinical trial participation should be considered as part of standard care.

scholarly journals Safety and Efficacy of First-Line Treatments for Chemotherapy-Naive Metastatic Castration-Resistant Prostate Cancer: A Systematic Review and Indirect Comparison

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Haofeng Zheng ◽  
Jialiang Chen ◽  
Wenhan Qiu ◽  
Sijie Lin ◽  
Yanxiong Chen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trials ◽  
Specific Antigen ◽  
Indirect Comparison ◽  
Progression Free Survival ◽  
Optimal Order ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Safety And Efficacy ◽  
Castration Resistant

Recently, several drugs have been introduced for the first-line treatment of chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC), but few studies have compared treatment outcomes directly. This indirect comparison among 10 clinical trials (n= 4870 patients) retrieved from PubMed, Web of Science, Cochrane Collaboration, and ClinicalTrails.gov was performed to assess the safety and efficacy of docetaxel, cabazitaxel, abiraterone, enzalutamide, and sipuleucel-T for the initial treatment of mCRPC. No significant differences in primary outcome (overall survival) were found among initial treatments. However, docetaxel had the highest probability (37.53%) of being the most effective, but at the cost of more adverse events, while enzalutamide was associated with the best secondary outcomes (prostate-specific antigen response, progression-free survival, quality of life, and adverse event profile). Thus, docetaxel is recommended as the first agent used for the chemotherapy of mCRPC, while enzalutamide is recommended as the first nonchemotherapy treatment. Additional clinical trials are needed to confirm these findings and establish the optimal order for multidrug treatment of mCRPC.

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