Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2016 Jul-Aug;18(4):586-91.
doi: 10.4103/1008-682X.177121.

Genomic predictors for treatment of late stage prostate cancer

Daniel H Shevrin  1
Affiliations
Review

Genomic predictors for treatment of late stage prostate cancer

Daniel H Shevrin. Asian J Androl. 2016 Jul-Aug.

Abstract

In spite of the development of new treatments for late stage prostate cancer, significant challenges persist to match individuals with effective targeted therapies. Genomic classification using high-throughput sequencing technologies has the potential to achieve this goal and make precision medicine a reality in the management of men with castrate-resistant prostate cancer. This chapter reviews some of the most recent studies that have resulted in significant progress in determining the landscape of somatic genomic alterations in this cohort and, more importantly, have provided clinically actionable information that could guide treatment decisions. This chapter reviews the current understanding of common alterations such as alterations of the androgen receptor and PTEN pathway, as well as ETS gene fusions and the growing importance of PARP inhibition. It also reviews recent studies that characterize the evolution to neuroendocrine tumors, which is becoming an increasingly important clinical problem. Finally, this chapter reviews recent innovative studies that characterize the compelling evolutionary history of lethal prostate cancer evidenced by polyclonal seeding and interclonal cooperation between metastasis and the importance of tumor clone dynamics measured serially in response to treatment. The genomic landscape of late stage prostate cancer is becoming better defined, and the prospect for assigning clinically actionable data to inform rationale treatment for individuals with this disease is becoming a reality.

PubMed Disclaimer

Figures

Figure 1
Figure 1
This graphical abstract outlines the multi-institutional integrative clinical sequencing analysis of samples from mCRPC individuals and depicts five pathways that harbor clinically actionable genomic alterations.
Figure 2
Figure 2
Pathway-guided treatment in prostate cancer. This diagram highlights pathways for targeting in prostate cancer.
Figure 3
Figure 3
This diagram outlines a path to genomics-driven treatments in prostate cancer. Because of the prevalence of PI3K pathway activation, ETS rearrangements, and androgen signaling, genomic enrichment of patients for these common disease subsets may follow traditional trial structures including combination treatments. For rare or private molecular disease subsets, these patients may be better suited for studies based on the specific molecular aberration. For all treatments, repeat biopsy will be valuable for evaluating mechanisms of resistance and evolution of clonal and subclonal genomic alterations.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Hussain M, Tangen CM, Berry DL, Higano CS, Crawford ED, et al. Intermittent versus continuous androgen deprivation in prostate cancer. N Engl J Med. 2013;368:1314–25. - PMC - PubMed
    1. Sweeney CJ, Chen YH, Carducci M, Liu G, Jarrard DF, et al. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. N Engl J Med. 2015;373:737–46. - PMC - PubMed
    1. James ND, Spears MR, Clarke NW, Dearnaley DP, de Bono JS, et al. Survival with newly diagnosed metastatic prostate cancer in the “docetaxel era”: data from 917 patients in the control arm of the STAMPEDE trial. Eur Urol. 2015;67:1028–38. - PubMed
    1. de Bono JS, Logothetis CJ, Molina A, Fizazi K, North S, et al. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med. 2011;364:1995–2005. - PMC - PubMed
    1. Beer TM, Armstrong AJ, Rathkopf DE, Loriot Y, Sternberg CN, et al. Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med. 2014;371:424–33. - PMC - PubMed