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Updated: Nov 18, 2025
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Clinical considerations for the management of androgen indifferent prostate cancer
Jacob E Berchuck1, Paul V Viscuse2, Himisha Beltran3
1Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Background:
Many systemic therapies for advanced prostate cancer work by disrupting androgen receptor signaling. Androgen indifferent prostate cancer (AIPC) variants, including aggressive variant prostate cancer (AVPC), neuroendocrine prostate cancer (NEPC), and double-negative prostate cancer (DNPC), are increasingly common and often overlapping resistance phenotypes following treatment with androgen receptor signaling inhibitors in men with metastatic castration-resistant prostate cancer and are associated with poor outcomes. Understanding the underlying biology and identifying effective therapies for AIPC is paramount for improving survival for men with prostate cancer.
Methods:
In this review, we summarize the current knowledge on AIPC variants, including our current understanding of the clinical, morphologic, and molecular features as well as current therapeutic approaches. We also explore emerging therapies and biomarkers aimed at improving outcomes for men with AIPC.
Results And Conclusions:
Establishing consensus definitions, developing novel biomarkers for early and accurate detection, further characterization of molecular drivers of each phenotype, and developing effective therapies will be critical to improving outcomes for men with AIPC. Significant progress has been made toward defining the clinical and molecular characteristics of AVPC, NEPC, and DNPC. Novel diagnostic approaches, including cell-free DNA, circulating tumor cells, and molecular imaging are promising tools for detecting AIPC in clinical practice. Building on previous treatment advances, several clinical trials are underway evaluating novel therapeutic approaches in patients with AIPC informed by an understanding of variant-specific biology. In this review, we discuss how these recent and ongoing studies will help to improve diagnosis, prognosis, and therapy for men with AIPC.
Insights
Androgen indifferent prostate cancer (AIPC) variants are resistant to standard treatments. Research is advancing diagnostics and therapies for these aggressive prostate cancer subtypes to improve patient survival.
Area of Science:
- Oncology
- Urology
- Molecular Biology
Background:
- Systemic therapies for advanced prostate cancer target androgen receptor signaling.
- Androgen indifferent prostate cancer (AIPC) variants, including aggressive variant prostate cancer (AVPC), neuroendocrine prostate cancer (NEPC), and double-negative prostate cancer (DNPC), represent resistance phenotypes.
- These AIPC variants are associated with poor outcomes in metastatic castration-resistant prostate cancer.
Purpose of the Study:
- To review current knowledge on AIPC variants, encompassing clinical, morphologic, and molecular features.
- To summarize existing therapeutic approaches for AIPC.
- To explore emerging therapies and biomarkers for improved AIPC outcomes.
Main Methods:
- Comprehensive literature review of AIPC variants.
- Analysis of clinical, morphologic, and molecular characteristics.
- Evaluation of current and emerging therapeutic strategies and biomarkers.
Main Results:
- Significant progress in defining clinical and molecular characteristics of AVPC, NEPC, and DNPC.
- Promising novel diagnostic approaches including cell-free DNA, circulating tumor cells, and molecular imaging for AIPC detection.
- Ongoing clinical trials evaluating novel, variant-specific therapies for AIPC.
Conclusions:
- Establishing consensus definitions and developing novel biomarkers are critical for improving AIPC outcomes.
- Advancements in diagnostics and understanding molecular drivers are key to early and accurate detection.
- Emerging therapies informed by variant-specific biology hold promise for improving diagnosis, prognosis, and treatment of AIPC.
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