Analysis of free-floating cancer DNA from blood samples has yielded leads for new prostate cancer treatment targets.

Using a commercially available “liquid biopsy” test in patients with advanced prostate cancer, researchers found a number of genetic changes in cell-free, circulating tumour DNA (ctDNA).

Cell-free ctDNA is tumour DNA that is circulating freely in the patient’s bloodstream. 

Cell-free ctDNA provides comprehensive information about all the different genetic changes in the tumour.

Today, treatments can sometimes be tailored to the genetic changes in a tumour, but these changes evolve over time.

The cell-free ctDNA tests can be used to track new genetic changes, and this information can be used to stop treatment to which resistance is emerging and to switch the patient to another treatment.

In the study, researchers found genetic changes linked to poor outcomes, as well as changes that appear to arise as tumours become resistant to therapy.

The changes in ctDNA found by the blood tests were similar to those previously reported in analyses of tumour tissue specimens, suggesting that ctDNA testing may be a viable alternative to tissue biopsy.

“This circulating tumour DNA test is now a valuable research tool to discover new molecular targets,” said lead study author Guru Sonpavde, MD, an associate professor of medicine at the University of Alabama in Birmingham, AL. “Eventually, it may also serve as a non-invasive alternative to the traditional tumour biopsy in cases where tissue biopsy is not safe or feasible. However, we’ll need a controlled, prospective clinical trial to confirm that selecting treatment based on the molecular information from this blood test improves patient outcomes.”

The Study

The researchers analysed cell-free ctDNA from blood samples of 514 patients with metastatic castration-resistant prostate cancer.

The blood test (Guardant360), which requires only two teaspoons of patient blood, examined changes in 70 cancer-related genes.

The association between DNA changes and clinical outcomes was explored in 163 patients.

In addition, the researchers explored how genomic changes evolved over time in 64 patients who underwent serial (periodic) blood tests.

Key Findings

Nearly all (94%) patients had at least one change detected in the ctDNA.

A higher overall number of genetic changes, including changes in the androgen receptor (AR) gene, were associated with poorer treatment outcomes, such as a tendency towards shorter survival (although the difference in survival was not statistically significant).

The genes that were most often mutated included TP53 (36%); AR (22%); APC (10%); NF1 (9%); EGFR, CTNNB1 and ARID1A (6% each); and BRCA1, BRCA2, and PIK3CA (5% each).

The most common genes with increased copy numbers were AR (30%), MYC (20%), and BRAF (18%) [increased cancer gene copy number can lead to overabundance of proteins that drive cancer growth].

Currently, there are no approved treatments for prostate cancer that target these specific genetic mutations, although several are being tested in clinical trials.

In the group of patients who underwent periodic blood tests, new changes in AR gene were particularly common.

According to the researchers, this finding suggests that developing treatments that target AR mutations may hold promise.

Source: ASCO