Breast cancer: scientists discover an on-off “switch” for metastasis
Despite advances in immunotherapies, more than 80% of advanced breast cancers do not respond to these therapies, leaving patients with limited options and facing the threat of metastasis. However, new research by a team at Stanford University and the Arc Institute has identified a key protein, called ENPP1, that could revolutionize breast cancer treatment.
The study, led by Stanford associate professor of biochemistry Lingyin Li and published in the Proceedings of the National Academy of Sciences on December 20, revealed that ENPP1 acts as an on/off switch that controls breast cancer resistance. breast to immunotherapy and its ability to metastasize. This new understanding could open the door to more effective therapies and better prediction of patient response to existing treatments.
Immunotherapies, such as pembrolizumab (Keytruda), have shown success in blocking interactions that dampen the immune system. However, its effectiveness depends on T cells, a type of immune cell, penetrating the tumor. Breast cancers and other “cold” tumor types lack T cell infiltration, making immunotherapies less effective.
Li’s research began with cGAMP, a molecule produced when cells’ DNA is damaged, as occurs in cancer cells. Li discovered that the ENPP1 protein eats up these molecular “danger” signals, thus keeping tumors cold. By analyzing ENPP1 levels in breast cancer patients, researchers found a direct correlation between elevated ENPP1 levels, resistance to immunotherapy, and a high probability of metastasis.
Most surprising was the conclusion that ENPP1 is not only crucial in primary tumors, but also in metastases, and its presence is not limited to cancer cells, but is also found in healthy cells around the tumor. “ENPP1 acts as a big dam at the top of the cascade,” Li explained, highlighting its critical role in blocking the immune response.
Also Read: American adults consume the equivalent of a meal in snacks, says study
The research team, in collaboration with the University of San Francisco, conducted mouse studies that showed that completely deleting ENPP1 or inhibiting its ability to chew up cGAMP in normal and cancer cells resulted in decreased tumor growth and metastasis. This confirmed that ENPP1 plays a crucial role in the STING pathway, a signaling cascade leading to immune response.
This discovery not only offers new hope for breast cancer patients, but also suggests that ENPP1 could play a key role in other types of “cold” tumors, such as lung cancer, glioblastoma, and pancreatic cancer. . Lingyin Li encourages doctors to further investigate the role of ENPP1 in patient outcomes.
Additionally, this advance allows doctors to use ENPP1 levels to personalize treatment and predict patient response to immunotherapy. Possibilities are also open for the development of drugs that target ENPP1, improving the effectiveness of existing therapies. Several ENPP1 inhibitors are already in clinical development.
In summary, this important discovery not only sheds light on breast cancer resistance to immunotherapy but also presents new opportunities for personalized treatment and improving the effectiveness of existing therapies in the fight against various types of cancers.” cold.” The research led by Lingyin Li marks a significant step towards a more precise and effective approach in the battle against cancer.
