Molecular alterations and emerging targets in castration resistant prostate cancer
1Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Downs Road, SM2 5PT Sutton, Surrey, UK.
Abstract:
Prostate cancer is the most common malignancy in Western Europe, of which approximately 10-20% presents with advanced or metastatic disease. Initial response with androgen deprivation therapy is almost universal, but progression to castration resistant prostate cancer (CRPC), an incurable disease, occurs in approximately 2-3 years. In recent years, the novel taxane cabazitaxel, the hormonal agents abiraterone and enzalutamide, the immunotherapeutic agent sipuleucel-T and the radiopharmaceutical radium-223 have been shown to prolong survival in large randomised trials, thus widely increasing the therapeutic armamentarium against the disease. Despite these advances, the median survival in the first-line setting of metastatic castration-resistant prostate cancer (mCRPC) is still up to 25 months and in the post-docetaxel setting is about 15-18 months. There is an urgent need for the development of biomarkers of treatment response, and for a deeper understanding of tumour heterogeneity and the molecular biology underlying the disease. In this review, we attempt to provide insight into the novel molecular targets showing promise in clinical trials.
Insights
Prostate cancer treatment faces challenges with castration-resistant disease progression. This review explores novel molecular targets to improve survival and understand treatment resistance in advanced prostate cancer.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- Prostate cancer is a leading malignancy in Western Europe, with 10-20% presenting as advanced or metastatic disease.
- While initial androgen deprivation therapy is effective, progression to incurable castration-resistant prostate cancer (CRPC) is common within 2-3 years.
- Recent therapeutic advances include cabazitaxel, abiraterone, enzalutamide, sipuleucel-T, and radium-223, yet median survival in metastatic CRPC remains limited.
Purpose of the Study:
- To review novel molecular targets for advanced prostate cancer.
- To provide insight into molecular mechanisms of treatment resistance.
- To identify promising therapeutic strategies for clinical trials.
Main Methods:
- Literature review of recent clinical trials and molecular studies.
- Analysis of therapeutic armamentarium against prostate cancer.
- Exploration of tumor heterogeneity and molecular biology.
Main Results:
- Several novel agents have demonstrated survival benefits in metastatic castration-resistant prostate cancer (mCRPC).
- Despite advances, significant unmet needs persist in improving survival, especially post-docetaxel treatment.
- Understanding tumor heterogeneity and molecular drivers is crucial for developing effective biomarkers and therapies.
Conclusions:
- There is an urgent need for biomarkers predicting treatment response in prostate cancer.
- Further research into molecular targets is essential for overcoming castration resistance.
- Novel therapeutic strategies are under investigation to improve outcomes for patients with advanced prostate cancer.
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