New Brunswick, N.J. – Investigators at Rutgers Cancer Institute of New Jersey have found that approximately 30 percent of men with localized prostate cancer may have alterations in DNA damage response pathways. Their research not only provides insight into the biology of prostate malignancies, but also it may expand treatment options for these patients. Namely a class of drugs known as PARP inhibitors, which inhibit a cancer cell’s ability to repair its own damaged DNA, may be effective for many patients with localized prostate cancer. Results of the work are being presented during the American Urological Association Annual Meeting taking place this week in Chicago.
Approximately one third of prostate cancer patients whose cancer has spread (metastatic) after treated with hormone therapy (castration resistant) have an abnormally regulated DNA damage response pathway. However, alteration rates in this pathway have not been fully characterized in patients whose cancer has not spread beyond the prostate (localized). Rutgers Cancer Institute Chief of Urologic Oncology Isaac Yi Kim, MD, PhD, MBA, Rutgers Robert Wood Johnson Medical School urology resident Arnav Srivastava, MD, MPH and colleagues further characterized these alteration rates.
Using The Cancer Genome Atlas database, which contained genetic information regarding hundreds of prostate cancers, investigators analyzed 12 genes of interest.. Survival analysis in patients with and without predictors of recurrence was carried out and further stratified by DNA damage response pathway status.
Of 455 patients, 136 (29.9 percent) had DNA damage response pathway alterations, most prominently alterations of the BRCA2 gene. When measured by Gleason score, a larger percentage of alterations were found in those with a Gleason score of 7 (49.3 percent) and 8 (44.1 percent) disease versus those with a Gleason score of 6 (6.6 percent). Survival analysis demonstrated worse survival among patients with DNA damage response pathway alterations in men with high-risk disease.
“Almost a third of patients with localized prostate cancer have these genetic alterations of interest. Patients with DDR pathway alterations may not only represent a high-risk subset of patients with localized prostate cancer, but also they may be the patients that benefit the most from therapeutic expansion of PARP inhibitors in prostate cancer,” notes Dr. Kim, who is the senior author on the work as well as a professor of surgery at Rutgers Robert Wood Johnson Medical School.
Other authors on the work are Isaac E. Kim, Jr., The Warren Alpert Medical School of Brown University, Rhode Island; Sinae Kim, Rutgers School of Public Health; Biren Saraiya and Tina Mayer, both Rutgers Cancer Institute and Rutgers Robert Wood Johnson Medical School; Mark N. Stein, Columbia University, New York; and Wun-Jae Kim, Chungbuk National University College of Medicine, Korea.
This work was supported by the Marion and Norman Tanzman Charitable Foundation. Additional information can be found at: https://doi.org/10.1097/01.JU.0000555713.66843.bf.
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