Targeted Therapy for Prostate Cancer

July 1, 2024

This page was reviewed under our medical and editorial policy by Wesley Yip, M.D., assistant professor, Division of Urology and Urologic Oncology, Department of Surgery, and Tanya Barauskas Dorff, M.D., professor, Department of Medical Oncology & Therapeutics Research, City of Hope^® Cancer Center Duarte

Targeted therapy refers to drugs that are designed to precisely target tumor cells while limiting damage to healthy cells. Several targeted therapies have become available for certain patients with advanced prostate cancer.

How Does Prostate Cancer Targeted Therapy Work?

Targeted therapies are drugs or other treatments designed to recognize features unique to specific cancer cells, such as abnormal genes or proteins that help the tumor cells survive and grow.

Like traditional chemotherapy, targeted therapies travel through the bloodstream, allowing them to hunt for cancer that has spread to distant sites in the body. But targeted therapies are more refined than standard chemotherapy drugs, which may be toxic to most cell types in the body, and often end up harming healthy tissue in addition to killing cancer cells.

Unlike traditional chemotherapies, targeted therapies are built to identify cancer cells (sparing healthy cells) and attack them in a precise way — by blocking a substance the cells need to divide and spread, for instance, or by changing proteins within the cells to destroy them.

That’s why targeted drug treatments have become a promising area of medicine for many types of cancer, including prostate cancer.

The main targeted therapies for prostate cancer are drugs known as PARP inhibitors.

PARP Inhibitors

These medications are designed to block a protein within tumor cells called PARP — short for poly (ADP-ribose) polymerase. In healthy cells, PARP helps repair DNA when it is damaged, which is a good thing. The problem is, cancer cells may also use PARP to fix DNA damage, helping them survive, make copies of themselves and spread. PARP inhibitors try to block cancer cells from using that repair system.

Certain patients may benefit from PARP inhibitors. The drugs are approved for people with metastatic prostate cancer that has not responded to hormonal therapy and also has specific genetic alterations that impede DNA repair. Tumor cells with those genetic changes are already hampered in their ability to fix DNA damage; treatment with a PARP inhibitor may further damage those tumor cells.

To determine whether a patient is a candidate for a PARP inhibitor, doctors perform one or more tests that look for altered DNA repair genes — either in a tumor sample or a blood sample. Research suggests those genetic changes are found in 20% to 30% of men with metastatic prostate cancer.

Four PARP inhibitors may be used for treating eligible patients with metastatic prostate cancer. The medications are taken by mouth, usually once or twice a day, and they are most often used along with some form of hormonal therapy.

Rucaparib (Rubraca^®): This drug may be an option for patients when the cancer has progressed despite treatment with a hormone-blocking agent and taxane chemotherapy (drugs such as docetaxel and cabazitaxel), and they carry an alteration in either of two particular DNA repair genes, called BRCA1 and BRCA2.

Olaparib (Lynparza^®): This medication may be used in either of two ways: along with the hormonal therapy abiraterone and the steroid drug prednisone, if a BRCA mutation is present; or by itself, if the patient has a mutation in a group of DNA repair genes known as HRR (which includes the BRCA genes) and the cancer has progressed despite treatment with abiraterone and enzalutamide (another hormone-blocking therapy).

Talazoparib (Talzenna^®): This drug, which is used along with enzalutamide, may be an option in the case of an HRR gene mutation.

Niraparib plus abiraterone acetate (Akeega^™): This medication combines the PARP inhibitor niraparib with abiraterone into a “dual-action” tablet given along with prednisone. It may be an option when the patient has a BRCA mutation.

These drugs were approved after PARP inhibitors were shown to slow the progression of metastatic prostate cancer. Patients receiving the drugs have typically lived longer without their cancer worsening, versus those given standard treatment that does not include a PARP inhibitor.

Targeted Therapy Side Effects

Although targeted therapy is engineered to limit harm to healthy body tissue, it may still have side effects. PARP inhibitors tend to carry similar side effects, some of the more common ones being:

• Nausea and/or vomiting
• Fatigue
• Lowered blood cell counts that may cause problems like anemia
• Appetite loss
• Constipation or diarrhea
• Cough or shortness of breath

In rare cases, some people treated with PARP inhibitors may develop a blood cancer, such as myelodysplastic syndrome or acute myeloid leukemia. Some men taking olaparib may also develop blood clots in the legs or lungs, which may be life-threatening. When discussing the possibility of starting a PARP inhibitor, patients should ask their doctor about both the pros and the cons of this prostate cancer treatment, including potential side effects.