Nerves in Prostate May Be New Treatment Target

New research shows that medications commonly used to control high blood pressure may help men reduce the effects of prostate cancer. While more study is required, and existing medications would need to be re-purposed, the results of these studies are very promising.

Prostate cancer is the second most frequently diagnosed cancer and the sixth leading cause of cancer death in men worldwide. According to the National Cancer Institute more than 16,000 new cases will be diagnosed this year alone. More than 25,000 men will die from the disease, accounting for 4.4 percent of all cancer deaths. Prostate cancer generally affects older men, grows slowly and is most often treatable. The most common form is adenocarcinoma which is treatable and generally not life-threatening. This type of prostate cancer can often be effectively removed by surgery or radiation.

The prostate is a small gland that is part of the male reproductive system. It produces a substance, PSA (prostate specific antigen) that plays a role in the fertilization process. Enzymes produced by the prostate help semen penetrate female eggs. As part of a regular checkup your doctor likely performs routine blood tests. One of the many things measured is your PSA. Excessive PSA production can be detected in the blood, and is a possible indicator of prostate disease.

The role of nerves in tumor growth

In 2013, Dr. Paul Frenette of the Albert Einstein Cancer Center, an extramural National Cancer Institute (NCI) center in New York, published a paper presenting the findings of a study that examined how nerves stimulate new blood vessels that can support prostate tumor growth.1 They reported that they could “short-circuit” this nerve stimulation to prevent new cancer-enabling blood vessels from forming. At that time they envisioned a new approach for treating prostate cancer through repurposing existing drugs knows to affect this process in other parts of the body.

In a new study from Einstein, now known as Montefiore Einstein Cancer Care, Dr. Frenette and colleagues sought to confirm their findings that “certain nerves sustain prostate cancer growth by triggering a switch that causes tumor vessels to proliferate.”1

Role of beta blockers

Beta blockers are medications you have probably heard of or perhaps already use to lower blood pressure. They are also called beta-adrenergic blocking agents. This means they work by blocking the effects of the hormone epinephrine, also known as adrenaline. Taking beta blockers makes your heart beat slower which lowers blood pressure. They also help blood vessels open wider and improve blood flow. The study results demonstrate that these medications people already take to treat hypertension “can kill cancer cells in tumors” of prostate cancer potentially by interrupting the nerve-stimulated blood vessel growth that occurs with the cancer.

Mice models

The 2017 study examined mice with prostate cancer. The researchers discovered that tumors have microenvironments. Nerve fibers may be involved in the regulation of those microenvironments but their specific job is not clear.

Increased cellular blood supply is associated with nerve and vascular development. Adrenaline-related signals from the nerves in the prostate cancer microenvironment support tumor growth by changing the blood vessel metabolism of certain cells.3 This means that new tumor growth may be able to be modified based upon the way energy is produced.

Cells rely on energy to grow and renew. Harvesting energy, the metabolic process, varies in different kinds of cells. The energy production in endothelial cells, cells that line the blood and lymphatic vessels, generally use a process called “oxidative phosphorylation” to create energy and stimulate blood vessels. In the mice models, researchers deleted the gene that codes for the binding receptors. They found that without the binding receptors cells were forced to rely almost exclusively on the process of glycolysis, a different way to generate energy. Dr. Frenette explained that oxidative phosphorylation generates more energy than glycolysis. This extra energy reduces endothelial cell function and inhibits angiogenesis—the formation of new blood vessels that result in progressive tumor growth.1

Conclusions

More research is needed as to the role that nerves play in prostate cancer tumor growth. Whether beta blockers can be repurposed to improve prostate cancer outcomes requires further investigation. Retrospective epidemiological studies conducted to date have identified that men with prostate cancer who were taking these medications had reduced the spread of cancer (metastasis) and longer survival.

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