New Pharmacotherapies in the Treatment of Advanced Prostate Cancer

2010 ◽  
Vol 4 ◽  
pp. CMU.S5075
Author(s):  
Walid El-Ayass ◽  
Joelle El-Amm ◽  
Maneesh Jain ◽  
Jeanny B. Aragon-Ching
Keyword(s):  
Prostate Cancer ◽  
Advanced Prostate Cancer ◽  
Standard Treatment ◽  
Locally Advanced ◽  
Castration Resistant Prostate Cancer ◽  
Clinical Safety ◽  
Treatment Practice ◽  
Castration Resistant ◽  
Prostate Cancer Therapy ◽  
The Right

Recent drug approvals in the field of prostate cancer therapy have brought about a change in the treatment landscape of locally advanced and metastatic castration-resistant prostate cancer. While this improvement offers a welcoming change in the standard treatment practice of prostate cancer, questions remain with regard to the proper sequencing of the right therapy for the appropriate patient. This review highlights the pre-clinical, safety and clinical studies that help bring to the forefront the drugs recently approved for the treatment of advanced prostate cancer and offer some insights to its use.

scholarly journals ZRSR2 overexpression is a frequent and early event in castration-resistant prostate cancer development

2021 ◽  
Author(s):  
Haiqing He ◽  
Jun Hao ◽  
Xin Dong ◽  
Yu Wang ◽  
Hui Xue ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle Progression ◽  
Locally Advanced ◽  
Patient Treatment ◽  
Early Event ◽  
Driver Gene ◽  
Castration Resistant Prostate Cancer ◽  
Driver Genes ◽  
Castration Resistant ◽  
Pdx Models

Abstract Background Androgen deprivation therapy (ADT) remains the leading systemic therapy for locally advanced and metastatic prostate cancers (PCa). While a majority of PCa patients initially respond to ADT, the durability of response is variable and most patients will eventually develop incurable castration-resistant prostate cancer (CRPC). Our research objective is to identify potential early driver genes responsible for CRPC development. Methods We have developed a unique panel of hormone-naïve PCa (HNPC) patient-derived xenograft (PDX) models at the Living Tumor Laboratory. The PDXs provide a unique platform for driver gene discovery as they allow for the analysis of differentially expressed genes via transcriptomic profiling at various time points after mouse host castration. In the present study, we focused on genes with expression changes shortly after castration but before CRPC has fully developed. These are likely to be potential early drivers of CRPC development. Such genes were further validated for their clinical relevance using data from PCa patient databases. ZRSR2 was identified as a top gene candidate and selected for further functional studies. Results ZRSR2 is significantly upregulated in our PDX models during the early phases of CRPC development after mouse host castration and remains consistently high in fully developed CRPC PDX models. Moreover, high ZRSR2 expression is also observed in clinical CRPC samples. Importantly, elevated ZRSR2 in PCa samples is correlated with poor patient treatment outcomes. ZRSR2 knockdown reduced PCa cell proliferation and delayed cell cycle progression at least partially through inhibition of the Cyclin D1 (CCND1) pathway. Conclusion Using our unique HNPC PDX models that develop into CRPC after host castration, we identified ZRSR2 as a potential early driver of CRPC development.

scholarly journals A A Canadian consensus forum on the management of patients with advanced prostate cancer

2019 ◽  
Vol 14 (4) ◽  
Author(s):  
Fred Saad ◽  
Christina Canil ◽  
Antonio Finelli ◽  
Sebastien J. Hotte ◽  
Shawn Malone ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Advanced Prostate Cancer ◽  
Castration Resistant Prostate Cancer ◽  
Research Education ◽  
Modified Delphi ◽  
Castration Resistant ◽  
Medical Oncologists ◽  
Oligometastatic Prostate Cancer ◽  
Scientific Group ◽  
High Level

Introduction: The management of advanced prostate cancer (PCa) continues to evolve with the emergence of new diagnostic and therapeutic strategies. As a result, there are multiple areas in this landscape with a lack of high-level evidence to guide practice. Consensus initiatives are an approach to establishing practice guidance in areas where evidence is unclear. We conducted a Canadian-based consensus forum to address key controversial areas in the management of advanced PCa. Methods: As part of a modified Delphi process, a core scientific group of PCa physicians (n=8) identified controversial areas for discussion and developed an initial set of questions, which were then reviewed and finalized with a larger group of 29 multidisciplinary PCa specialists. The main areas of focus were non-metastatic castration-resistant prostate cancer (nmCRPC), metastatic castration-sensitive prostate cancer (mCSPC), metastatic castration-resistant prostate cancer (mCRPC), oligometastatic prostate cancer, genetic testing in prostate cancer, and imaging in advanced prostate cancer. The predetermined threshold for consensus was set at 74% (agreement from 20 of 27 participating physicians). Results: Consensus participants included uro-oncologists (n=13), medical oncologists (n=10), and radiation oncologists (n=4). Of the 64 questions, consensus was reached in 30 questions (n=5 unanimously). Consensus was more common for questions related to biochemical recurrence, sequencing of therapies, and mCRPC. Conclusions: A Canadian consensus forum in PCa identified areas of agreement in nearly 50% of questions discussed. Areas of variability may represent opportunities for further research, education, and sharing of best practices. These findings reinforce the value of multidisciplinary consensus initiatives to optimize patient care.

scholarly journals The Current Landscape of Treatment in Non-Metastatic Castration-Resistant Prostate Cancer

2019 ◽  
Vol 13 ◽  
pp. 117955491983392 ◽  
Author(s):  
Joelle El-Amm ◽  
Jeanny B Aragon-Ching
Keyword(s):  
Prostate Cancer ◽  
Drug Administration ◽  
Advanced Prostate Cancer ◽  
Unmet Need ◽  
Early Data ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Castration Resistant ◽  
Fda Approval ◽  
Variable Potential

Non-metastatic castration-resistant prostate cancer (nmCRPC) is a heterogeneous disease with variable potential in developing into overt metastases. It is an area of increased unmet need in advanced prostate cancer and for which there had been no great treatments until recent US Food and Drug Administration (FDA) approval of 2 novel anti-androgens apalutamide and enzalutamide, which were both approved given benefit in metastasis-free survival. Early data on the use of darolutamide, another novel anti-androgen, are also explored. This review discusses the pivotal trials that led to the approval of apalutamide and enzalutamide in the nmCRPC setting and discusses the key promises and challenges with the use of these agents.

scholarly journals New Developments in the Treatment of Castration-Resistant Prostate Cancer

2014 ◽  
Vol 12 (5S) ◽  
pp. 773-776
Author(s):  
Celestia S. Higano
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial Data ◽  
Annual Conference ◽  
Castration Resistant Prostate Cancer ◽  
New Developments ◽  
Castration Resistant ◽  
Therapeutic Decisions ◽  
Clinical Scenarios ◽  
Hormonal Therapies ◽  
The Right

During the past 4 years, a host of new agents have been approved for the treatment of patients with advanced prostate cancer. As a result, selecting the right agent for the right patient at the right time is a clinical challenge. At the NCCN 19th Annual Conference, Dr. Celestia Higano explored the rationale behind such therapeutic decisions and the supporting clinical trial data. She reviewed the different classes of therapeutic agents, from immunotherapy and hormonal therapies to chemotherapy and radioisotopes, and offered suggestions for the clinical scenarios in which they may be used most successfully.

Therapeutic Approach to Castration-resistant Prostate Cancer

2009 ◽  
Vol 05 (01) ◽  
pp. 83
Author(s):  
Fred Saad ◽  
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Androgen Deprivation Therapy ◽  
Therapeutic Approach ◽  
Advanced Prostate Cancer ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Resistant Form ◽  
Near Future ◽  
The Continuum

Androgen deprivation therapy (ADT) has been and continues to be the most common treatment for men with advanced prostate cancer and is now used earlier in the continuum of care for prostate cancer. Unfortunately, the majority of prostate cancer patients on ADT will develop a castration-resistant form of the disease that is responsible for the majority of the morbidity and mortality related to prostate cancer. Given recent advances, there are now therapeutic options available that can reduce the morbidity and improve survival in patients with castrationresistant prostate cancer (CRPC). Research is intensifying in this area and further improvements can be expected in the near future. This review will briefly summarize what is currently available and propose strategies for the management of CRPC.

scholarly journals Assessment of Health-Related Quality of Life in Patients with Advanced Prostate Cancer—Current State and Future Perspectives

Cancers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 147
Author(s):  
Alexander Kretschmer ◽  
Roderick C. N. van den Bergh ◽  
Alberto Martini ◽  
Giancarlo Marra ◽  
Massimo Valerio ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Prostate Cancer ◽  
Advanced Prostate Cancer ◽  
Health Related Quality ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Clinical Scenarios ◽  
Related Quality ◽  
Health Related

With the therapeutic landscape of advanced prostate cancer rapidly evolving and oncological benefits being shown for a plethora of new agents and indications, health-related quality of life (HRQOL)-associated evidence is still subpar. In the current comprehensive review, we discuss the importance of HRQOL for patients with advanced PC (metastatic hormone-sensitive prostate cancer (mHSPC), metastatic castration-resistant prostate cancer (mCRPC) and non-metastatic castration-resistant prostate cancer (nmCRPC)), and present the most frequently used tools to evaluate HRQOL in recent randomized trials. Furthermore, we discuss the ease of use of these validated questionnaires for clinicians and try to focus on the suggested appropriate use in clinical practice, as well as potential strategies for improvement of HRQOL evaluation in these clinical scenarios of advanced prostate cancer.

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