PARP inhibitors are a type of targeted treatment that can be used for some people with prostate cancer. These medications take advantage of specific weaknesses in cancer cells, particularly cells that have certain genetic changes that affect how they repair damaged DNA.
We recently spoke with Jefferson Health’s Dr. Kevin Zarrabi, a prostate cancer expert and researcher, about how PARP inhibitors work, who may benefit from them, and why genetic testing is an important part of determining whether these treatments are an option.
What are PARP inhibitors?
Your cells are constantly repairing damage to their DNA. Several different proteins and pathways help with this process. PARP proteins are involved in one of the ways cells repair DNA damage.
PARP inhibitors block the activity of PARP proteins. This can make it harder for a cancer cell to repair DNA damage and survive.
Some prostate cancer cells already have problems with another DNA-repair pathway because of inherited or acquired genetic changes. When both repair mechanisms are disrupted, the cancer cell may be unable to repair enough DNA damage to survive.
This is why PARP inhibitors are considered a targeted treatment: they are most useful when the biology of the tumor suggests that the cancer is particularly vulnerable to blocking PARP.
Who can benefit from PARP inhibitors?
PARP inhibitors are generally used for people whose prostate cancer has certain genetic changes associated with sensitivity to these medications. BRCA1 and BRCA2 are two of the best-known examples, but they aren’t the only genes that can matter.
Dr. Zarrabi explains that there is a broader group of DNA-repair genes that may make prostate cancer sensitive to PARP inhibitors. “It’s that same genetic subset, BRCA2, BRCA1, and there are more genes,” he says. In fact, he notes that “20-plus genes” may potentially confer sensitivity to these treatments.
The specific genetic alteration matters because not every mutation has the same effect on treatment response. Your oncology team can use genetic and tumor testing to determine whether your cancer has an alteration that could make a PARP inhibitor an appropriate option.
When are PARP inhibitors used in prostate cancer?
PARP inhibitors were initially studied extensively in people with more advanced prostate cancer, but their use has expanded as research has shown benefits in different treatment settings.
According to Dr. Zarrabi, PARP inhibitors can now be used in some people with metastatic hormone-sensitive prostate cancer, meaning prostate cancer that has spread and requires treatment that works throughout the body. They can also be used later, including as a third-, fourth- or fifth-line treatment, depending on the individual’s cancer and previous treatments.
“Basically, you can use a PARP inhibitor right now at any point, as long as you have one of the mutations like a BRCA2 or BRCA1 that predict that you’re going to respond favorably,” Dr. Zarrabi says.
The exact timing and choice of PARP inhibitor depends on factors such as your genetic results, where and how extensively the cancer has spread, previous treatments, and your overall treatment plan.
PARP inhibitors may be combined with other treatments
PARP inhibitors aren’t always used alone. Researchers are studying whether combining them with other prostate cancer treatments can provide additional benefits. Dr. Zarrabi notes that “we’re now using PARP inhibitors actually in combination with things like ARPIs, which are some of the backbone therapies in prostate cancer.”
PARP inhibitors may be combined with androgen receptor pathway inhibitors, or ARPIs. ARPIs are an important part of treatment for many people with advanced prostate cancer because they block signals involving male hormones that prostate cancer cells can use to grow.
Clinical trials are also exploring PARP inhibitors in combination with other approaches, including radioligand therapies. These combinations are an area of ongoing research, so they may not be appropriate or available for everyone outside of a clinical trial.
Why is genetic testing so important?
Genetic testing can help identify people whose tumors may be sensitive to these medications.
The test looks for genetic changes that are present in the tumor itself, as well as inherited genetic changes that are present throughout the body. These tests provide different types of information, and your care team may recommend one or both depending on your diagnosis and treatment situation.
Dr. Zarrabi emphasizes that genetic testing remains an important step in making PARP inhibitors available to the people who may benefit from them. “That is one of the rate-limiting steps,” he said, because “in order to receive a PARP inhibitor, you do have to receive genetic testing, which remains underutilized.”
If you have metastatic prostate cancer, ask your oncology team whether genetic testing and tumor testing are appropriate for you.
What does this mean for you?
PARP inhibitors have become an important targeted treatment option for some people with advanced prostate cancer, particularly those whose cancer has genetic changes that make it more vulnerable to these medications.
As Dr. Zarrabi explains, “PARP inhibitors work in prostate cancer, especially those who have the mutations.” Research is also continuing to identify new ways to use these medications and determine which combinations may be most effective.
For people whose tumors have the right biology, PARP inhibitors may offer meaningful benefits. “When the biology of the tumor dictates it is going to be sensitive to it,” Dr. Zarrabi said, PARP inhibitors “can really provide a survival benefit for those patients.”
If you have prostate cancer, ask your care team whether genetic testing could help identify treatment options based on the specific biology of your cancer.
Disclaimer: The information provided in this article is for informational purposes only and is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Outcomes4Me is not acting as your caregiver, and any suggestions or guidance offered should not replace the advice of your healthcare provider or qualified medical professional. Always seek the guidance of your physician or other qualified health provider with any questions you may have regarding a medical condition.
