Targeted Therapy for Prostate Cancer

As researchers have learned more about some of the changes inside prostate cancer cells that help them grow, they have developed newer types of drugs that target these changes.

How targeted drugs work

Targeted drugs attack specific parts of cancer cells that make them different from normal cells. This is different from chemotherapy (chemo) and hormone therapy. Targeted drugs sometimes work when these other types of drugs don’t, and they often have different side effects.

Like chemo and hormone therapy, these drugs enter the bloodstream and reach almost all areas of the body, which makes them useful against some cancers that have spread to distant parts of the body.

PARP inhibitors

PARP (poly(ADP)-ribose polymerase) enzymes are proteins inside cells that normally help repair damaged DNA.

Some other proteins inside cells (including the BRCA1 and BRCA2 proteins) also help repair DNA, but in a different way. Changes (mutations) in genes that code for one of these DNA repair proteins can stop them from working like they should.

Drugs called PARP inhibitors, which block the PARP proteins, make it very hard for tumor cells with an abnormal DNA repair gene (including a BRCA1 or BRCA2 gene change) to repair their damaged DNA, which often leads to the death of these cells.

These drugs are only likely to be helpful if the cancer cells have changes in certain DNA repair genes called homologous recombination repair (HRR) genes. These include BRCA1, BRCA2, ATM, ATR, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCA, FANCL, MLH1, MRE11A, NBN, PALB2, RAD51B, RAD51C, RAD51D, and RAD54L.

Your doctor will likely test your blood or your cancer cells to be sure the cells have a DNA repair gene change before starting treatment with a PARP inhibitor.

These drugs are taken by mouth as pills or capsules, typically once or twice a day. They are given along with some type of hormone therapy, such as an LHRH agonist or after an orchiectomy.

Side effects of PARP inhibitors

Common side effects of these drugs include nausea, vomiting, diarrhea, fatigue, loss of appetite, low red blood cell counts (anemia), constipation, skin rash, abnormal liver blood tests, low blood platelet counts, cough, and shortness of breath. Other side effects are also possible.

Rarely, some people treated with these drugs might develop a blood cancer later on, such as myelodysplastic syndrome or acute myeloid leukemia.

Some men taking olaparib might develop blood clots in the lungs or legs.

AKT inhibitors

Some prostate cancer cells have a change in a gene called PTEN. When cells lose PTEN, a growth signal inside the cell called AKT can become too active. This helps cancer cells survive and keep growing, even during hormone therapy.

Drugs called AKT inhibitors block this signal. This can help slow the growth of cancer cells that have lost PTEN.

Capivasertib (Truqap) can be used with abiraterone and prednisone to treat prostate cancer that has spread but still responds to hormone therapy, if the cancer cells have lost the PTEN gene. Your doctor will test your cancer cells for this gene loss before starting treatment. As with abiraterone alone, men who haven't had their testicles removed also need to keep taking an LHRH agonist or antagonist.

Capivasertib is taken as a pill, twice a day for 4 days, then 3 days off. This 7-day cycle then repeats.

Side effects of capivasertib

Common side effects include high blood sugar, diarrhea, and skin rash. Doctors check blood sugar often during treatment, especially in men with diabetes or who are overweight. This drug can also harm an unborn baby, so partners who could get pregnant should use effective birth control during treatment.

PSMA-targeted radiopharmaceutical therapy

Lutetium Lu 177 vipivotide tetraxetan (Pluvicto) is a radiopharmaceutical. This means it's a drug that carries a small amount of radiation straight to cancer cells. It attaches to a protein called PSMA (prostate-specific membrane antigen), found on the surface of most prostate cancer cells. Once attached, it releases radiation that kills the cancer cell.

Doctors use this drug to treat:

• Metastatic androgen pathway modulation-resistant prostate cancer (mAPMR), also called metastatic castration-resistant prostate cancer (mCRPC), after the cancer has grown despite hormone therapy and, in most cases, chemotherapy
• Metastatic androgen pathway modulation-naïve or -sensitive prostate cancer (mAPMN/S), also called metastatic hormone-sensitive prostate cancer, given together with another hormone therapy drug called an androgen receptor pathway inhibitor (ARPI)

A special PET scan can show whether the cancer cells have enough PSMA for this treatment to work.

Doctors give this drug as an IV infusion. Most men get one dose every 6 weeks, for up to 6 doses.