Towards precision oncology in advanced prostate cancer
Related Experiment Video
Updated: Jan 6, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Sheng-Yu Ku1, Martin E Gleave2, Himisha Beltran3
1Division of Medical Oncology, Dana Farber Cancer Institute, Boston, MA, USA.
Abstract:
Metastatic biopsy programmes combined with advances in genomic sequencing have provided new insights into the molecular landscape of castration-resistant prostate cancer (CRPC), identifying actionable targets, and emerging resistance mechanisms. The detection of DNA repair aberrations, such as mutation of BRCA2, could help select patients for poly(ADP-ribose) polymerase (PARP) inhibitor or platinum chemotherapy, and mismatch repair gene defects and microsatellite instability have been associated with responses to checkpoint inhibitor immunotherapy. Poor prognostic features, such as the presence of RB1 deletion, might help guide future therapeutic strategies. Our understanding of the molecular features of CRPC is now being translated into the clinic in the form of increased molecular testing for use of these agents and for clinical trial eligibility. Genomic testing offers opportunities for improving patient selection for systemic therapies and, ultimately, patient outcomes. However, challenges for precision oncology in advanced prostate cancer still remain, including the contribution of tumour heterogeneity, the timing and potential cooperation of multiple driver gene aberrations, and diverse resistant mechanisms. Defining the optimal use of molecular biomarkers in the clinic, including tissue-based and liquid biopsies, is a rapidly evolving field.
Insights
Genomic sequencing reveals molecular targets and resistance mechanisms in advanced prostate cancer. This precision oncology approach improves patient selection for targeted therapies and clinical trials, enhancing outcomes.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Castration-resistant prostate cancer (CRPC) presents complex molecular characteristics.
- Advances in genomic sequencing have illuminated the landscape of CRPC.
- Understanding resistance mechanisms is crucial for effective treatment.
Purpose of the Study:
- To identify actionable molecular targets in CRPC.
- To explore emerging resistance mechanisms in CRPC.
- To translate genomic insights into clinical practice for improved patient selection.
Main Methods:
- Metastatic biopsy programs.
- Genomic sequencing technologies.
- Analysis of DNA repair aberrations (e.g., BRCA2 mutations).
- Assessment of mismatch repair defects and microsatellite instability.
- Identification of prognostic features (e.g., RB1 deletion).
Main Results:
- Genomic profiling identifies targets for PARP inhibitors, platinum chemotherapy, and checkpoint inhibitor immunotherapy.
- BRCA2 mutations guide selection for specific therapies.
- Mismatch repair defects/microsatellite instability correlate with immunotherapy response.
- RB1 deletion indicates poor prognosis and may inform therapeutic strategies.
Conclusions:
- Genomic testing enhances patient selection for systemic therapies in advanced prostate cancer.
- Precision oncology in CRPC faces challenges including tumor heterogeneity and resistance mechanisms.
- Optimizing the use of molecular biomarkers, including liquid and tissue biopsies, is an evolving clinical field.
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:56Treatment Resistant Cancers
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
01:21Cancer Survival Analysis