Dr Armstrong’s team is also examining CTC biomarkers “beyond AR” to identify new candidate tests and drug targets, he told Cancer Therapy Advisor.

Among promising prostate cancer biomarkers in development are DNA damage-repair gene mutations such as BRCA1, BRCA2, and ATM obtained from traditional tumor biopsy samples, Dr Antonarakis said.


Continue Reading

These “may predict sensitivity to PARP inhibitors such as olaparib,” he explained.

Somatic or germline DNA damage-repair gene mutations occur in up to 20% of patients with prostate cancer, Dr Antonarakis and coauthors noted in a recent review of emerging prostate cancer biomarkers.5

PI3K/PTEN/Akt pathway-activation biomarkers and WNT signaling pathway gene aberrations are also undergoing study as molecular biomarkers that could inform prostate cancer treatment decision-making.

The search is also under way for prostate cancer RNA biomarkers, Dr Pentyala noted.5 “A recent discovery of a long noncoding RNA SChLAP1 in the prostate has provided a novel biomarker that not only adds to the ability to identify prostate cancer, but also to conventional risk stratification,” he and coauthors noted in a recent review.

The promise of DNA and RNA biomarkers is not limited to treatment selection. These tools might also prove to be a practical diagnostic tool for detecting prostate cancer at earlier tumor stages, when treatment is more effective.

“SChLAP1 has been clinically validated for the prognosis of aggressive prostate cancer and integration of genomic tests may advance the diagnosis of prostate cancer through early identification of high-risk patients,” Dr Pentyala and coauthors noted in their recent review.

When CTCs and ctDNAs are detectable, blood tests should become a “preferred choice” for early-stage diagnosis of prostate cancer, Dr Pentyala said. “We are also working on urine-based tests to see whether we can detect tumor cells sloughing off into urine from the prostate.”

“CTCs and ctDNAs reflect tumor uniqueness [and] the variation between individuals and help in targeting the specific type of tumor with therapeutics,” Dr Pentyala said.  “My only concern is, at what stage do CTCs and ctDNAs start appearing in blood. Some tumors do not shed cells as they are localized and enclosed, particularly in the prostate.”

At least until liquid biopsies’ accuracy exceeds that of tumor biopsies, however, tumor biopsy will continue to be the gold standard in characterizing prostate cancers. “If liquid biopsies are validated with 100% specificity and 100% sensitivity, they will definitely replace cumbersome tumor biopsies,” said Dr Pentyala.

References

  1. Beltran H, Antonarakis ES, Morris MJ, Attard G. Emerging molecular biomarkers in advanced prostate cancer: translation to the clinic. Am Soc Clin Oncol Educ Book. 2016;35:131-141.
  2. SEER Stat Fact Sheets: Prostate Cancer. US National Cancer Institute (NCI). http://seer.cancer.gov/statfacts/html/prost.html. Accessed June 22, 2016.
  3. Scher HI, Lu D, Schreiber NA, et al. Association of AR-V7 in circulating tumor cells as a treatment-specific biomarker with outcomes and survival in castration-resistant prostate cancer. JAMA Oncol. 4 Jun 2016. doi:10.1001/jamaoncol.2016.1828 [Epub ahead of print]
  4. Leibrand CR, Price DK, Figg WD. Androgen receptor splice variant 7 (AR-V7) and drug efficacy in castration-resistant prostate cancer: biomarker for treatment selection exclusion or inclusion? Cancer Biol Ther. 2016;17(5):467-469.
  5. Pentyala S, Whyard T, Pentyala S, et al. Prostate cancer markers: an update. Biomed Rep. 2016;4(3):263–268.