A receptor tyrosine kinase in HER2+ breast cancer metastasis

A receptor tyrosine kinase in HER+ breast cancer metastasis

A research team has uncovered a protein that, once deactivated, could prevent the development of metastases in an aggressive type of cancer, HER2-positive breast cancer as in the journal Cell Reports.

A cancerous tumor develops when cells proliferate at an abnormally high rate and agglomerate in healthy tissue. Some of these cells are even more cunning. "Sometimes, cancer cells manage to leave the tumor to spread in the body, which complicates the evolution of the disease," said the senior author.

These cells move more easily than most of their peers. They detach from the tumor, enter the bloodstream and reach other organs, for example the lungs, bones or the brain. Called 'metastatic cells,' they are more difficult to destroy as they spread to other parts of the body and are more resistant to current treatments; 90 per cent of breast-cancer deaths are caused by metastases. Hence, one priority in oncology is to prevent tumor cells from spreading because it has the potential of saving many lives.

Researchers have taken a step towards actually blocking metastases. In their study, the team demonstrated that a protein, AXL, influences the occurrence of metastasis in HER2-positive cancer, an aggressive type that accounts for 20 per cent of breast cancers. In HER2-positive breast cancers, cells with high levels of AXL are more likely to detach from tumors to form metastases. Authors found that AXL is expressed in HER2+ cancers displaying epithelial-to-mesenchymal transition (EMT) signatures where it contributes to sustain EMT.

The research was done on mice and with samples of tumor cells taken from cancer patients. Interfering with AXL in a patient-derived xenograft (PDX) impaired transforming growth factor β (TGF-β)-induced cell invasion. Also, pharmacological inhibition of AXL specifically decreased the metastatic burden of mice developing HER2+ breast cancer.

Statistical indicators about patients are also encouraging. In women with HER2-positive cancer, it was found that the less AXL is present, the better the survival rate. Previously, researchers had linked the AXL protein to another type of cancer, triple negative breast cancer, but no one had previously examined its presence in HER2-positive cancer.

It has already been shown that the action of AXL can be hindered. The researchers administered an AXL-inhibiting drug therapy to mice with HER2-positive tumors and found that metastases were less prone to develop. The drug is currently being tested in clinical trials for various therapeutic uses. If subsequent studies are as successful, this treatment could also be used to treat breast cancer patients. It would act as a complement to therapies targeting the HER2-positive tumor.

nouvelles.umontreal.ca/en/article/2018/05/07/breast-cancer-discovery-of-a-protein-linked-to-metastasis/

https://www.cell.com/cell-reports/abstract/S2211-1247(18)30548-5

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