Tests Using Heart Medicines in Mice May Spur Future Treatments for Men with Prostate Cancer

Grantee: Isabel R. Schlaepfer, PhD
Area of Focus: Insulin resistance
Grant Term: 2017-2021

The Challenge: In prostate cancer, excess body weight acts like a line of defense for the tumor, blocking the immune cells from getting to the tumor to destroy it. The fat cells have a “self-sacrificing protection,” meaning they’re metabolized by the cancer for energy. Because of this, the cancer continues to grow, becomes more aggressive, and spreads. And the immune cells “give up in defeat.”

What cancer researchers are looking for now is a way to re-engage the immune cells to attack the tumors again.

The first immunotherapy vaccine approved to treat advanced prostate cancer that is no longer responding to hormone therapy is called sipuleucel-T (Provenge). This vaccine stimulates immune cells to help it attack prostate cancer cells, but the vaccine cannot cure the cancer. Another type of immunotherapy  called immune checkpoint inhibitor can be used to treat prostate cancer that has come back  or that has spread.

Finding a safe and better way to reboot the immune cells against prostate cancer is a critical need and a promising area of new research.

The Research: American Cancer Society (ACS) research grantee, Isabel Schlaepfer, PhD, is working with mice in a lab to better understand how prostate cancer metabolizes excess fat, using it as an energy source to keep growing.

Schlaepfer’s lab team reported findings in a recently published study using mice with prostate cancer to study the effect of ranolazine, a heart drug that’s used to ease chest pain (angina), against prostate cancer. They provided evidence that ranolazine can block the growth of prostate cancer in mice by blocking the metabolism of fat, which decreases how the tumor uses fat as a “food source.”

They discovered this heart drug also stimulates the mouse’s immune response against prostate cancer by increasing the presence of immune cells in the tumor and its microenvironment.

It’s not yet known if the anti-tumor effect of ranolazine in mice persists after the drug treatment ends.

Why Does It Matter? Schlaepfer is one of the first researchers to study metabolic inhibitors and their role in the immune system and prostate cancer. Her newly found knowledge about the role of fat metabolism in the communication between tumor and immune cells can also be explored with certain breast, ovarian, and colon cancers.  These cancers, like prostate cancer, rely on the gene CPT1A (carnitine palmitoyl transferase 1A) to regulate fat metabolism.