Abstract
Prostate cancer continues to impose a significant health burden worldwide and in the United States, with rising incidence, persistent mortality rates, and disparities in both incidence and patient outcomes. Advances in genomic profiling have highlighted the remarkable heterogeneity of prostate cancer, revealing frequent alterations in key oncogenes, tumor suppressors, and pathways such as androgen receptor signaling and DNA damage repair that drive disease progression and therapy resistance. These molecular discoveries and their mechanistic validation in laboratory and preclinical models are transforming prostate cancer management, enabling more precise, biomarker-driven treatments and clinical trials. However, challenges, including intra- and inter-tumor genomic diversity, remain formidable barriers to progress. This review provides an overview of the current genomic landscape of prostate cancer and discusses recent advances in precision therapy. We also discuss emerging directions in integrating molecular profiling with personalized patient care, while addressing the roadblocks hampering progress. The discussion highlights the critical need for continued innovation in the development of personalized therapies to improve the clinical outcomes for patients with prostate cancer.
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Acknowledgements
All figures in this manuscript were created with BioRender.com. We thank fellow clinicians, researchers, and all other members of the GU Cancer Working Group at the UMMC CCRI for their insightful discussion on the components presented in this manuscript. We would also like to acknowledge the funding support from the Department of Defense (HT9425-23-1-0452; W81XWH-22-1-0913) and the Cancer Center and Research Institute.
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Ajay P. Singh and John C. Henegan conceived and designed the manuscript. John A. Ligon conducted the literature review, performed data analysis, and prepared the first draft. Shashi Anand, Seema Singh, Jawed Siddiqui, John C. Henegan, and Ajay P. Singh reviewed the draft and suggested revisions, including the addition of relevant literature. Shashi Anand and Seema Singh contributed to the graphic design. John A. Ligon and Shashi Anand prepared the final revised version of the manuscript. All authors reviewed and approved the final manuscript for submission.
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Ligon, J.A., Anand, S., Singh, S. et al. Genomic landscape and precision therapy in prostate cancer: current status and future directions. npj Precis. Onc. (2026). https://doi.org/10.1038/s41698-026-01368-3
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DOI: https://doi.org/10.1038/s41698-026-01368-3


