Biomarker-guided treatment for prostate cancer?

While there is still no cure for cancer, diagnosing and treating prostate cancer has come a long way. The innovations and advancements in the prostate cancer market have made significant strides which have helped doctors, and even more importantly, their patients.


Prostate Cancer Detection

Innovations in prostate cancer detection can be seen such as with the PSA test, which may soon be replaced by a new blood test called the PHI (Prostate Health Index) test as it is becoming more widely available throughout the country. The PHI test is three times more specific in detecting prostate cancer than the PSA test. And the newly available biopsy technique called the MRI-guided prostate biopsy defeats the standard transrectal ultrasound biopsy in the accuracy and precision of detecting prostate cancer as is uses MRI to pinpoint suspicious lesions. 

Biomarkers for Prostate Cancer

Despite these advancements, there is still one major tool that is missing: biomarker-guided treatment. None of the current tools and techniques to diagnose and treat prostate cancer require molecular testing to help select patients for treatment. Being that we are currently in a state of making tools and techniques more precise, you would think this would already be available. But this may soon change as researchers in the United Kingdom are working on making biomarker-guided treatment available for prostate cancer. 

Researchers in the UK discovered during a phase 1B trial that men with pretreated metastatic castration-resistant prostate cancer who had certain gene mutations were more likely to respond to treatment with an oral drug called olaparib, compared to men with prostate cancer who did not have the same gene mutations. Olaparib is a PARP inhibitor which has been approved in the U.S. for treating ovarian cancer in women who have BRCA mutations.

In a TOPARP-A trial consisting of 49 patients, 16 responded to olaparib. According to Dr. Joaquin Mateo, MD, four of these men responded to olaparib for more than a year. He said this is "quite a big achievement for a later-stage population." Dr. Mateo is a fellow at the institute of Cancer Research in London and the lead author of the study. 

Genomic Testing Prostate Cancer

Researchers used genomic testing to identify the molecular sensitivity to an oral drug called olaparib. Through sequencing, they detected gene mutations associated with DNA repair in tumors and were able to pinpoint the most notable mutations. They found that 15 of the 49 men were "biomarker positive", and of these 15 men, 13 of them responded to olaparib. This means that anyone who responded to the drug were most likely biomarker positive. 

"We hope that this is a step toward the molecular stratification of treatment for prostate cancer," said Dr. Mateo.

Dr. Mateo says more is to be done. He plans to take the next step in validating olaparib in prostate cancer trials in the next trial called TOPARP-B. In this trial, only patients who screen positive for the DNA-repair mutations linked to response in TOPARP-A will be enrolled in the study. 

How might olaparib work for prostate cancer? Olaparib is a PARP inhibitor, and tumors that lack BRCA function are sensitive to PARP inhibitors. Prostate cancers are associated with certain gene mutations, such as BRCA2, ATM, and CHEK2. All of these are sensitive to PARP inhibitors. 

As for how many men have these genetic mutations associated with prostate cancer, Dr. Mateo claims prior research shows that BRCA2 is present in about 12 percent of prostate cancers, whileATM is present in about 7 percent of prostate cancers. BRCA2 and ATM are the most common genetic mutations associated with prostate cancer.