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Updated: Oct 7, 2025
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Biomarkers of Response to Neoadjuvant Androgen Deprivation in Localised Prostate Cancer
Maree Pechlivanis1, Bethany K Campbell1, Christopher M Hovens1
1Department of Surgery, University of Melbourne, Parkville, VIC 3050, Australia.
Abstract:
Prostate cancer (PCa) is a hormone driven cancer, characterised by defects in androgen receptor signalling which drive the disease process. As such, androgen targeted therapies have been the mainstay for PCa treatment for over 70 years. High-risk PCa presents unique therapeutic challenges, namely in minimising the primary tumour, and eliminating any undetected micro metastases. Trials of neoadjuvant androgen deprivation therapy aim to address these challenges. Patients typically respond well to neoadjuvant treatment, showing regression of the primary tumour and negative surgical margins at the time of resection, however the majority of patients relapse and progress to metastatic disease. The mechanisms affording this resistance are largely unknown. This commentary attempts to explore theories of resistance more broadly, namely, clonal evolution, cancer stem cells, cell persistence, and drug tolerance. Moreover, it aims to explore the application of these theories in the PCa setting. This commentary also highlights the distinction between castration resistant PCa, and neoadjuvant resistant disease, and identifies the markers and characteristics of neoadjuvant resistant disease presented by current literature.
Insights
Prostate cancer treatment faces challenges with therapy resistance. This commentary explores mechanisms like clonal evolution and cancer stem cells contributing to treatment failure in high-risk prostate cancer.
Area of Science:
- Oncology
- Cancer Biology
- Translational Research
Background:
- Prostate cancer (PCa) is driven by androgen receptor signaling, making androgen-targeted therapies a long-standing treatment.
- High-risk PCa requires minimizing primary tumors and eliminating micrometastases, addressed by neoadjuvant androgen deprivation therapy (ADT).
- While neoadjuvant ADT initially shows tumor regression, most patients eventually relapse due to resistance.
Purpose of the Study:
- To explore theories of treatment resistance in prostate cancer.
- To apply concepts like clonal evolution, cancer stem cells, cell persistence, and drug tolerance to PCa.
- To differentiate between castration-resistant PCa and neoadjuvant-resistant disease.
Main Methods:
- Literature review and commentary on existing theories of cancer resistance.
- Analysis of current literature on markers and characteristics of neoadjuvant-resistant PCa.
- Exploration of the application of resistance theories within the prostate cancer context.
Main Results:
- Neoadjuvant ADT in high-risk PCa often leads to initial tumor response but is followed by widespread relapse.
- Mechanisms underlying resistance to neoadjuvant therapy remain largely undefined.
- The commentary identifies key theoretical frameworks for understanding PCa treatment resistance.
Conclusions:
- Understanding resistance mechanisms is crucial for improving high-risk prostate cancer outcomes.
- Distinguishing neoadjuvant resistance from castration resistance is important for targeted therapeutic strategies.
- Further research into clonal evolution, cancer stem cells, and drug tolerance is needed to overcome PCa treatment failure.
