Tomasz M. Beer, MD, FACP
Having a deeper understanding of the genetic makeup of patients with castration-resistant prostate cancer would open the door to novel treatments, both monotherapy and combination regimens, explains Tomasz M. Beer, MD, FACP.
Additionally, while still in its early stages, integrative genomic testing could be the future for personalizing therapy for CRPC. A recent example includes the discovery of BRCA
mutations within CRPC, Beer says. While BRCA
mutations are mostly associated with breast and ovarian cancers, this discovery could provide a new avenue for treating patients with CRPC.
In an interview with OncLive
, Beer, deputy director, Knight Cancer Institute, Oregon Health and Science University, discusses the current state of genetic testing for prostate cancer and what emerging approaches are currently being explored in clinical trials.
OncLive: What is currently known about the genetics of prostate cancer?
: What we are beginning to see in the field is the delivery on the promise of personalized therapy selection in patients with advanced metastatic castration-resistant prostate cancer. What's happening is that several groups are analyzing individual patient's tumors, typically from a metastatic site biopsy, and deeply sequencing the genetic material from those cancers. This is enabling us to really understand what the defects and abnormalities are that are responsible for cancer growth and progression.
There is a lot of work left to be done. We haven't solved the whole puzzle, but there have been some exciting discoveries about abnormalities that were unexpected. If these findings are confirmed, these could have real implications for specific treatments for those patients.
What were some of the discovered abnormalities that would be able to advance the treatment paradigm?
The most interesting and compelling discovery was the presence of DNA repair defects. Most commonly and best known in the DNA repair defect world are the BRCA
genes, or the genes that are the breast cancer susceptibility genes. Many people have heard of these genes as the ones that, when inherited, put a woman at a high risk for developing breast cancer. It turns out that these genes can also play a role in prostate cancer. They are present in 20% of advanced prostate cancers.
About half of those 20% of patients inherit the BRCA
genes, which was a surprise. The other half were acquired, which means that the tumor ends up having a mutation in that gene even though the patient has normal genetic makeup, which was also a surprise. The important part about that is there are drugs that are potentially quite effective in treating cancers that have these defects. A companion study from the United Kingdom reported a very high response rate to agents called PARP inhibitors in patients who harbor these mutations.
A discovery has been made that was unexpected, which is that essentially breast cancer mutations play a role in a significant minority of prostate cancers. Studies are beginning to show that there might be effective therapies for those patients, which are therapies that we would never ordinarily prescribe in prostate cancer.
How will a better understanding of the genetics help expand the current treatment armamentarium for prostate cancer?
We're not quite there yet. Anytime we have exciting genomic news, patients will come in and ask, "Can I have this test? Can I have this therapy?" It's not quite ready yet. A lot of these tests in prostate cancer are still investigational. There is not a clinical-grade whole genome that is easy to obtain and affordable. A little more time and work needs to be done before these tests are readily available.