Common transplant drug inhibits breast cancer growth

Tacrolimus, a drug that is commonly used to prevent organ transplantation rejection, inhibits breast cancer growth in pre-clinical studies. The finding from UNC scientists was reported in the May 26 Public Library of Science.

Nancy Klauber-DeMore, MD, associate professor of surgery, said, “We now have a rationale for performing human clinical trials to determine if Tacrolimus reduces breast cancer growth in humans. Since Tacrolimus is already an FDA-approved drug, the safety and toxicity profile is known, which means that Tacrolimus could potentially go directly into a later stage clinical trial.”

Klauber-DeMore is a member of UNC Lineberger Comprehensive Cancer Center and co-founder and Chief Scientific Officer of Enci Therapeutics, Inc., a UNC spin-off biotech company.

Tacrolimus is used to prevent rejection, which occurs when a recipient’s immune system attacks the transplanted organ. Tacrolimus is in a class of medications called immunosuppressants. Tacrolimus works by decreasing immune system activity by binding to and inactivating a protein called calcineurin in immune cells.

Although preventing organ transplant rejection and inhibiting cancer growth may seem unrelated, the team realized that activating calcineurin is a common pathway that stimulates both the immune system and the growth of new blood vessels to tumours. Blocking blood vessel growth to tumours is a therapeutic strategy to inhibit tumour growth.

Klauber-DeMore’s group had previously discovered that a protein called SFRP2 stimulates blood vessel growth and is expressed in human breast cancers. While investigating the mechanism through which SFRP2 stimulates blood vessel growth, they found that SFRP2 activates calcineurin in blood vessel cells. Based on this mechanism, Klauber-DeMore thought that Tacrolimus might also bind to and inactivate calcineurin in blood vessel cells, thereby blocking new blood vessel growth to tumours. The team tested this theory in a pre-clinical breast tumour model and found that orally administered Tacrolimus inhibited breast tumour growth rate by over 70 percent.

Klauber-DeMore said, “This data is encouraging, but we don’t know yet whether Tacrolimus will inhibit breast cancer growth in humans. However, this pre-clinical study provides a reasoning for the next step, which will be to perform a clinical trial using Tacrolimus in patients with breast cancer.”

Side effects of Tacrolimus can be severe and include infection, cardiac damage, hypertension, blurred vision, liver, and kidney problems. Patients need to be monitored carefully and the dose is adjusted as needed.

(Source: UNC School of Medicine)

More Information

For more information on breast cancer, types of breast cancer and its investigations and treatments, as well as some useful videos, see Breast Cancer.