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Developing Personalized Treatment for Triple-Negative Breast Cancer Patients

Triple-negative breast cancer is very aggressive and has no specific treatment. Researchers discovered that the activation of interferon-gamma signaling plays a role in the progression and spread of the disease. The findings will help doctors to develop a personalized treatment plan for patients depending on their cancer subtype.

Immunotherapies have worked well for many types of cancers, but the response from triple-negative cancer patients has been very low and slow. Researchers attribute the low response to molecular details.  That’s why they used a mouse model to show that losing the ELF5 protein promotes the activity of interferon-gamma receptor 1.

Stabilized gamma receptor 1 activates interferon-gamma signaling, which then increases tumor aggression and spread. Therapeutics can be used to block the interferon-gamma signaling.

In a study, scientists found that when triple-negative breast cancer tumors in mice lost the ELF5 protein function, their course of disease looked similar to that of human patients. The disease became very aggressive and metastatic when the mice lost ELF5.

On examining the RNA expressed in the triple-negative breast tumor cells in mice that lost the ELF5 expression, they found increased activity of the interferon-gamma pathway, which may have been caused by the increased expression of the protein receptor.

The loss also caused the accumulation of neutrophils, which is an immune cell that has an immune suppressive function. Healthy mammary cells that retained ELF5 had reduced levels of interferon-gamma signaling.

They blocked the signaling using an antibody against the interferon-gamma receptor 1 or by manipulating the tumor cells genetically to express low levels of the receptor. This made the tumors to grow and spread slowly.

To determine if their findings were applicable to humans, the researchers analyzed the genetic and protein data. From the patients to evaluate their level of interferon-gamma receptor expression and ELF5. Patients with high receptor levels and low ELF5 did not do well since their cancers spread immediately in their bodies.

This shows that patients should be targeted selectively when applying treatment. Some with low ELF5 may need immunotherapy together with interferon-gamma signaling blocking therapy.

The research team is planning to study the immunology of triple-negative breast cancer and examine the role that different immune cells play in driving cancer aggression and metastasis.

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