Understanding Androgen Receptor Pathway Inhibitors For Prostate Cancer

“[There are] small amounts of testosterone made by the adrenal gland and fat stores that can still stimulate the prostate cancer to grow. These drugs [ARPIs] either block the testosterone from getting in the cells … or decrease the production of testosterone from the fat stores or adernal glands,” Dr. William Kevin Kelly, chair of the Department of Medical Oncology at Thomas Jefferson University’s Sidney Kimmel Medical College in Philadelphia, tells SurvivorNet.

Prostate cancer cells grow by “listening” to hormones, especially androgens, with testosterone being the main one. Standard treatments, such as leuprolide or goserelin, work by stopping the testicles from producing androgens, thereby removing the growth stimulus for the cancer cells. However, small amounts of androgens are still produced by the adrenal gland, fat tissue, and sometimes inside the tumor itself, which can be enough to feed and promote the growth of malignant cells.

This is where ARPIs come in. This class of medication closes this loophole, providing a more comprehensive and effective hormone blockade.

How ARPIs Work

ARPIs target the same growth pathway from a different angle. Drugs like enzalutamide, apalutamide, and darolutamide bind to the androgen receptor inside the cancer cell and prevent the hormone from activating it.

At first, these medicines were approved only for men whose tumors had already learned to grow despite very low testosterone (the “castration‑resistant” stage). When researchers moved them earlier — right when metastatic prostate cancer is diagnosed — the survival benefit became much larger. That’s why, for most men with newly diagnosed metastatic disease today, the standard is androgen deprivation therapy plus an ARPI from the start.

“What we found is that all these drugs were approved in late-stage prostate cancer, so in hormone-refractory prostate cancer. But, as we moved it up further and further to earlier therapy, the improvement in survival has increased dramatically. So, the most standard therapy right now is when they are diagnosed with metastatic prostate cancer,” Dr. Kelly explains.

Taking An ARPI: What To Expect

Adding an ARPI to your treatment usually means more effective control of the cancer, more time before you need the next treatment, and typically a longer life.

It is worth noting that no therapy is side-effect-free. In this situation, deepening hormone blockade can increase side effects you hear about with ADT, such as:

• Weight gain
• Higher cholesterol or blood sugar
• Bone thinning
• Fatigue
• Sexual dysfunction
• Mood or memory changes

Fortunately, these side effects can often be easily managed.

Your role as a patient is to stay aware and proactive. Blood work and frequent follow-ups will be required to ensure that the treatment is working. Lifestyle changes, like prioritizing exercise, a heart‑healthy diet, calcium and vitamin D intake, and strength training, are not “extras,” they are part of treatment. Many men feel fine for the first few months and only later (around 6-9 months in) start to notice fatigue, weight redistribution, or mood changes, so these are topics you may need to revisit at later doctor appointments.

Questions To Ask Your Doctor

• How long will I stay on this therapy?
• What side effects should I expect, and when should I contact my healthcare providers?
• Do I need to have an appointment with a therapist due to potential mood changes?
• Does this therapy interact with my medications for other conditions?
• How do I know if these medications are working out?

Content independently created by SurvivorNet with support from Novartis Pharmaceuticals Corp.

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