By Drs. David Niesel and Norbert Herzog, Medical Discovery News
Prostate cancer is the second most common cancer in men behind skin cancer. Scientists have sequenced the genetic information of prostate tumors from 150 men with an advanced form of that cancer called metastatic castration-resistant prostate cancer, or MCRPC. Results have revealed that 89 percent of them had genetic mutations that could be targeted with existing drugs or drugs currently in clinical trials. It also revealed that MCRPC is fundamentally different than primary prostate cancer and requires different therapies depending on the genetic mutations in each tumor. Ultimately, the study established that prostate cancer is not a single disease but rather a group of diseases with differing genetic changes that drive it.
The American Cancer Society estimated that over 200,000 men developed new cases of prostate cancer and nearly 28,000 died from it last year. That makes it the second leading cause of cancer deaths in men after lung cancer. Prostate cancer primarily occurs in older men as the average age of diagnosis is about 66. Prostate cancer can be serious, but most men do not die from it because in many cases it progresses slowly. More than 2.9 million men in the US are living with this disease.
Previous studies to determine mutations in early-stage prostate cancer uncovered changes in more than eight different genes. However, thus far, these results have not been useful in guiding treatment or in determining prognosis. For this new MCRPC study, scientists used image-guided biopsies to get tumor samples from sites to which the cancer had spread. Samples were obtained from lymph nodes, livers, other soft tissue and bones of patients. They also determined the sequence of each patient's normal DNA from non-cancerous tissue. To get enough different samples, this study involved eight institutions in the US and Europe.
About one-fifth of the MCRPC patients had mutations in BRCA1 and BRCA2, the same genes that are linked to breast and ovarian cancer in women. This opens the door for treating prostate tumors with drugs currently used to treat BRCA-associated breast cancers such as PARP inhibitors, which interfere with cancer cells' ability to repair their DNA and causing them to die. Patients with these BRCA mutations should also seek genetic counseling to determine the possible risk to other family members. Other non-BRCA prostate tumors also had other mutations that could be targeted with drugs currently used to treat other types of cancer.
Going forward, these researchers will sequence the genomes from prostate tumors of 500 individuals and will monitor their treatments and outcomes for several more years. This will help correlate specific mutations and the response or resistance to specific treatments, learning which treatments are best for which kind of tumors.
Tumors of the lung, breast and colon are already routinely sequenced to help determine the proper treatment options. Identifying the mutations in individual prostate cancers will allow for more effective personalized medical treatments.
Medical Discovery News is hosted by professors Norbert Herzog at Quinnipiac University, and David Niesel of the University of Texas Medical Branch. Learn more at www.medicaldiscoverynews.com.