Journal: NPJ precision oncology
This review article synthesizes current knowledge on the genomic landscape of prostate cancer and its implications for precision oncology.
Key points:
- • Disease burden and disparities: Prostate cancer incidence is rising globally and in the U.S., with mortality remaining substantial. The article emphasizes persistent racial and geographic disparities in both incidence and outcomes.
- • Genomic heterogeneity: Comprehensive genomic profiling has revealed marked inter- and intra-tumoral heterogeneity. Frequent alterations are seen in:
- • Oncogenes and tumor suppressors
- • Androgen receptor (AR) signaling pathways
- • DNA damage repair (DDR) pathways
These changes underlie disease progression, metastasis, and treatment resistance.
- • Mechanistic insights and models: Laboratory and preclinical models have validated how specific genomic alterations drive biology and resistance, helping to connect molecular findings to functional consequences in prostate cancer.
- • Precision therapy and biomarker-driven care: Molecular discoveries are increasingly integrated into:
- • Targeted and biomarker-selected treatments
- • Rationally designed clinical trials
- • More refined patient stratification and risk assessment
- • Challenges and limitations: Despite progress, major obstacles include:
- • Significant genomic diversity within and between tumors
- • Complexity of resistance mechanisms
- • Barriers to broad, equitable implementation of molecular testing in routine practice
- • Future directions: The authors highlight emerging strategies to:
- • More deeply integrate molecular profiling into personalized treatment decisions
- • Optimize clinical trial design around genomic subsets
- • Innovate new targeted and combination therapies
Overall, the review argues that while genomic insights are reshaping prostate cancer management, sustained innovation and better translation into practice are essential to meaningfully improve patient outcomes.