An experimental therapy has shown promising results in fighting a particularly aggressive breast cancer with limited treatment options.

A recent study has revealed that the novel treatment decreased the growth and spread of triple-negative breast cancer in mice. The approach uses a protein to block two growth mechanisms that help the breast cancer cells multiply and migrate. The protein, which has the name tubulointerstitial nephritis antigen-like 1 (TINAGL1), occurs naturally in the body. The study suggests that a synthetic, or recombinant, version of TINAGL1 could reduce the growth and spread of triple-negative breast cancer. A report on the findings now features in the journal Cancer Cell.

"People have tried," says senior study author Yibin Kang, a professor of molecular biology at Princeton University in Princeton, NJ, "to block the spread of this form of cancer, but attempts so far have failed because if you try one approach, the cancer cells compensate by finding a way to escape."

"With this new approach, the treatment blocks both pathways at the same time," he adds.

Triple-negative breast cancer

Breast cancer is a disease that develops when cells in breast tissue grow abnormally and multiply. The hormones estrogen and progesterone and excess levels of human epidermal growth factor receptor 2 (HER2) protein are known drivers of breast cancer. By testing samples of breast cancer tissue for hormone receptors and HER2 levels, doctors can recommend therapies that work by reducing the strength of these drivers.

Around two-thirds of breast cancers will test positive for either estrogen or progesterone receptors or both. Around 20% will test positive for excess HER2. However, in 12% to 17% of people who receive a breast cancer diagnosis, the test will be negative for both hormone receptors and high HER2. In other words, it will be triple-negative.

Treatment options for triple-negative breast cancer are limited, as the cancer is unlikely to respond to hormone therapy such as tamoxifen or HER2 therapy such as trastuzumab. Triple-negative breast cancers also tend to be more aggressive. They are more likely to spread to other parts of the body and come back following treatment.

TINAGL1 works in two ways

The recent study suggests that synthetic TINAGL1 could be a promising candidate for a much-needed new triple-negative breast cancer treatment.

One way that TINAGL1 works is by reducing the activity of epidermal growth factor receptor (EGFR) protein. Certain mutations in the EGFR gene increase growth signals to cells to promote tumor growth and spread. However, treatments that target EGFR in triple-negative breast cancer usually result in the cancer cells finding alternative growth pathways.

The other way that TINAGL1 works is by interfering with a pathway involving the protein focal adhesion kinase (FAK) and a group of molecules called integrins. This interference upsets the ability of the cancer cells to grow, migrate, stick to each other, and establish new tumors in other parts of the body.

Strong links between TINAGL1 and outcomes

In the first part of the study, the investigators examined more than 800 samples of human breast tumors. They found that samples from people with more advanced tumors and shorter survival times had lower levels of TINAGL1. Samples from people with better outcomes, however, tended to have higher levels of TINAGL1. These links were particularly strong in tissue that came from people with triple-negative breast cancers.

When they engineered mouse cancer cells to express high levels of TINAGL1, the researchers found that the resulting tumors grew more slowly and were less likely to spread to the lung. Giving TINAGL1 to mice with breast cancer for 7 weeks also halted tumor growth and spread to the lungs, with no significant adverse effects. The treatment was still effective when the mice received it after tumors had started to spread.

The authors conclude:

"Our results suggest [TINAGL1] as a candidate therapeutic agent for [triple-negative breast cancer] by dual inhibition of integrin/FAK and EGFR signaling pathways."