scholarly journals CPT1A Supports Castration-Resistant Prostate Cancer in Androgen-Deprived Conditions

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1115 ◽  
Author(s):  
Joshi ◽  
Stoykova ◽  
Salzmann-Sullivan ◽  
Dzieciatkowska ◽  
Liebman ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Histone Acetylation ◽  
Specific Inhibitor ◽  
Dependent Manner ◽  
Castration Resistant Prostate Cancer ◽  
Lipid Catabolism ◽  
Castration Resistant ◽  
Common Cancer ◽  
Androgen Withdrawal

Prostate cancer (PCa) is the most common cancer in men, and the global burden of the disease is rising. The majority of PCa deaths are due to metastasis that are highly resistant to current hormonal treatments; this state is called castration-resistant prostate cancer (CRPC). In this study, we focused on the role of the lipid catabolism enzyme CPT1A in supporting CRPC growth in an androgen-dependent manner. We found that androgen withdrawal promoted the growth of CPT1A over-expressing (OE) tumors while it decreased the growth of CPT1A under-expressing (KD) tumors, increasing their sensitivity to enzalutamide. Mechanistically, we found that CPT1A-OE cells burned more lipid and showed increased histone acetylation changes that were partially reversed with a p300 specific inhibitor. Conversely, CPT1A-KD cells showed less histone acetylation when grown in androgen-deprived conditions. Our results suggest that CPT1A supports CRPC by supplying acetyl groups for histone acetylation, promoting growth and antiandrogen resistance.

AR Copy Number and AR Signaling-directed Therapies in Castrationresistant Prostate Cancer

2018 ◽  
Vol 18 (9) ◽  
pp. 869-876
Author(s):  
Samanta Salvi ◽  
Vincenza Conteduca ◽  
Cristian Lolli ◽  
Sara Testoni ◽  
Valentina Casadio ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Copy Number ◽  
Clinical Trial Design ◽  
Complete Information ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Anti Cancer ◽  
Hormone Sensitive ◽  
Predictive And Prognostic Biomarker

Background: Adaptive upregulation of Androgen Receptor (AR) is the most common event involved in the progression from hormone sensitive to Castration-Resistant Prostate Cancer (CRPC). AR signaling remains the main target of new AR signalling-directed therapies such as abiraterone and enzalutamide in CRPC patients. Objective: In this review, we discuss general mechanisms of resistance to AR-targeted therapies, with a focus on the role of AR Copy Number (CN). We reported methods and clinical applications of AR CN evaluation in tissue and liquid biopsy, thus to have a complete information regarding its role as predictive and prognostic biomarker. Conclusion: Outcomes of CRPC patients are reported to be highly variable as the consequence of tumor heterogeneity. AR CN could contribute to patient selection and tumor monitoring in CRPC treated with new anti-cancer treatment as abiraterone and enzalutamide. Further studies to investigate AR CN effect to these agents and its potential combination with other prognostic or predictive clinical factors are necessary in the context of harmonized clinical trial design.

scholarly journals Interplay Between SOX9, Wnt/β-Catenin and Androgen Receptor Signaling in Castration-Resistant Prostate Cancer

2019 ◽  
Vol 20 (9) ◽  
pp. 2066 ◽  
Author(s):  
Namrata Khurana ◽  
Suresh C. Sikka
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Signaling Pathways ◽  
Critical Role ◽  
Castration Resistant Prostate Cancer ◽  
Form Complex ◽  
Androgen Receptor Signaling ◽  
Castration Resistant ◽  
Signaling Axis

Androgen receptor (AR) signaling plays a key role not only in the initiation of prostate cancer (PCa) but also in its transition to aggressive and invasive castration-resistant prostate cancer (CRPC). However, the crosstalk of AR with other signaling pathways contributes significantly to the emergence and growth of CRPC. Wnt/β-catenin signaling facilitates ductal morphogenesis in fetal prostate and its anomalous expression has been linked with PCa. β-catenin has also been reported to form complex with AR and thus augment AR signaling in PCa. The transcription factor SOX9 has been shown to be the driving force of aggressive and invasive PCa cells and regulate AR expression in PCa cells. Furthermore, SOX9 has also been shown to propel PCa by the reactivation of Wnt/β-catenin signaling. In this review, we discuss the critical role of SOX9/AR/Wnt/β-catenin signaling axis in the development and progression of CRPC. The phytochemicals like sulforaphane and curcumin that can concurrently target SOX9, AR and Wnt/β-catenin signaling pathways in PCa may thus be beneficial in the chemoprevention of PCa.

The role of abiraterone in the management of metastatic castration-resistant prostate cancer

2012 ◽  
Vol 12 (4) ◽  
pp. 429-437 ◽  
Author(s):  
Alex Rawlinson ◽  
Aza Mohammed ◽  
John Beatty ◽  
Richard Bell ◽  
Marek Miller
Keyword(s):  
Prostate Cancer ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant

scholarly journals Angiogenesis and Anti-Angiogenic Treatment in Prostate Cancer: Mechanisms of Action and Molecular Targets

2021 ◽  
Vol 22 (18) ◽  
pp. 9926
Author(s):  
Evangelia Ioannidou ◽  
Michele Moschetta ◽  
Sidrah Shah ◽  
Jack Steven Parker ◽  
Mehmet Akif Ozturk ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trials ◽  
Chemotherapeutic Agents ◽  
Combination Therapies ◽  
Mechanisms Of Resistance ◽  
Marginal Benefit ◽  
Antiangiogenic Activity ◽  
Castration Resistant ◽  
Common Cancer

Prostate cancer (PC) is the most common cancer in men and the second leading cause of cancer-related death worldwide. Many therapeutic advances over the last two decades have led to an improvement in the survival of patients with metastatic PC, yet the majority of these patients still succumb to their disease. Antiagiogenic therapies have shown substantial benefits for many types of cancer but only a marginal benefit for PC. Ongoing clinical trials investigate antiangiogenic monotherapies or combination therapies. Despite the important role of angiogenesis in PC, clinical trials in refractory castration-resistant PC (CRPC) have demonstrated increased toxicity with no clinical benefit. A better understanding of the mechanism of angiogenesis may help to understand the failure of trials, possibly leading to the development of new targeted anti-angiogenic therapies in PC. These could include the identification of specific subsets of patients who might benefit from these therapeutic strategies. This paper provides a comprehensive review of the pathways involved in the angiogenesis, the chemotherapeutic agents with antiangiogenic activity, the available studies on anti-angiogenic agents and the potential mechanisms of resistance.

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