British researchers have developed what they call a three-in-one blood test for advanced prostate cancer — one that helps doctors select an initial treatment, check whether it is working, and monitor the disease long term.
The test grew out of research on levels of cancer DNA in patients’ blood, which scientists call circulating DNA levels. Higher levels can indicate the disease is progressing.
Researchers developed the test to help doctors tailor therapies for prostate cancer stemming from an inherited BRCA gene mutation. They hope it leads to treatment improvements.
Researchers from two London research facilities — the Institute of Cancer Research and the Royal Marsden National Health Services Foundation Trust — conducted the study. The article they wrote, “Circulating Free DNA to Guide Prostate Cancer Treatment with PARP Inhibition,” was published in the journal Cancer Discovery,
The team obtained blood samples from 49 advanced prostate cancer patients enrolled in the Phase 2 TOPARP-A clinical trial (NCT01682772). The trial is assessing whether the PARP inhibitor Lynparza (olaparib) is effective against advanced cases of the cancer.
The London researchers learned that some patients responded to Lynparza, some failed to respond, and some responded, then stopped.
The circulating DNA in patients who responded to Lynparza fell in half after only eight weeks, the team discovered. In contrast, circulating DNA rose by 2 percent in patients who failed to respond to the therapy.
In addition, patients who responded to Lynparza survived much longer than those who failed to respond — 17 months, versus 10.
Researchers did a genetic analysis of the cancer cells in patients who stopped responding. They found that some cells changed in a way that interfered with DNA repair. This was particularly true in cells with BRCA2 and PALB2 genes that had initially allowed the cancer to be susceptible to Lynparza.
The blood test that evolved from the research will enable doctors to identify advanced prostate cancer patients who could benefit from PARP inhibitors like Lynparza. Doctors can also use it to check patients’ response to medication so non-responders can be switched to other therapies as soon as possible. Finally, the test can be used to monitor cancer cells for genetic changes that indicate the cancer is becoming resistant to treatment.
“Our study identifies, for the first time, genetic changes that allow prostate cancer cells to become resistant to the precision medicine olaparib,” Dr. Johann de Bono, a professor at the Institute of Cancer Research, said in a press release. “From these findings, we were able to develop a powerful, three-in-one test that could in future be used to help doctors select treatment, check whether it is working, and monitor the cancer in the longer term. We think it could be used to make clinical decisions about whether a PARP inhibitor is working within as little as four to eight weeks of starting therapy.
“Not only could the test have a major impact on treatment of prostate cancer, but it could also be adapted to open up the possibility of precision medicine to patients with other types of cancer as well,” he concluded.