Breast cancer: discovery of a switch to block metastases

In 2023, in mainland France, 61,214 new cases of breast cancer will be detected. According to the latest 2023 figures from Panorama of cancers in France, it is the most common in women, representing 33% of malignant tumors, and the deadliest. The development of effective treatments is therefore a very important issue.

The ENPP1 protein acts on immunotherapy

In a new study published in the journal Proceedings of the National Academy of Sciencesresearchers from Stanford University and of the Arc Institute found that a protein called ENPP1 could act as an on/off switch to block metastasis and control breast cancer’s ability to resist immunotherapy.

ENPP1 is a protein produced by cancer cells as well as healthy cells in and around the tumor. To test its role in breast cancer, researchers tested it with an immunotherapy called Keytruda, whose active ingredient is pembrolizumab. This treatment works by using T lymphocytes, which enter the tumor.

This medication is only effective on so-called “hot” tumors, such as melanoma and certain lung cancers. For other cancers, such as breast and pancreatic cancer, the tumors are called “cold,” meaning that T cells cannot access the tumor. The team’s goal was to understand whether ENPP1 could affect the effectiveness of immunotherapy for cold tumors such as breast cancer.

Results: Scientists found that breast cancer patients who had high levels of ENPP1 did not respond favorably to immunotherapy treatments and had a high risk of metastasis. In contrast, those with lower ENPP1 levels had a better response to immunotherapy and no metastasis.

A protein like a switch to block metastases

In other words, the more researchers reduce ENPP1 levels, the more the chances increase for patients: they respond better to immunotherapy treatments, have fewer – or even no – metastases that develop and their probability of relapse decreases.

Finally, the researchers conducted a final experiment on mice to see what happened if they completely turned off the ENPP1 switch. To do this, they eliminated the ENPP1 protein from the rodents’ bodies and observed a reduction in the growth of tumors and metastases. This means that lowering ENPP1 levels is positive for patients, but so is eliminating ENPP1.

Ultimately, ENPP1 could therefore be used in the context of new immunotherapies. “Our study should offer hope to everyone“, assures Lingyin Lione of the authors, in a communicated.