New hope for treatment-resistant breast cancer

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By: Laura Tennant

More effective treatments for an aggressive treatment-resistant form of breast cancer known as HER2+ breast cancer may be on the horizon, according to new research from the Université de Montréal.

The study, which was published in PNAS, found a promising potential target for treating HER2+ breast cancer. The team was led by professor Jean-François Côté and his doctoral student Marie-Anne Goyette at the cytoskeleton organization and cell-migration research unit of the UdeM-affiliated Montreal Clinical Research Institute.

“Our study provides new evidence [for] a therapeutic target in HER2+ breast cancer metastasis,” Côté said.

HER2 stands for human epithelial growth factor 2. HER2+ breast cancer is an aggressive form of the disease associated with treatment resistance and a poor prognosis. Approximately 20 per cent of breast cancer is HER2+, according to the Canadian Breast Cancer Network.

Human epithelial growth factor 2 is a protein on the cell surface that promotes growth. When breast cancer cells are positive for HER2, the cancer cells overexpress the HER2 gene, leading to faster growth and a higher chance of metastasis.

Cancer can become life-threatening when it metastasizes, spreading to other organs and systems in the body. If the cancer is able to invade these other systems, it can then begin to shut down essential bodily functions.

Tumours tend to become treatment-resistant and metastasize when their immediate environment is hypoxic, or low in oxygen. Low oxygen leads to rapid tumour growth, as well as a weakened immune response. Hypoxia is known to cause resistance to treatments like radiotherapy and chemotherapy.

The Université de Montréal research team targeted a protein called AXL that helps tumours form the low-oxygen environment conducive to growth, metastasis and treatment resistance.

The researchers deleted or “knocked out” the AXL gene in mice with HER2+ breast cancer. Mice without the AXL gene showed reduced hypoxia, normalized blood vessels and increased activity in the body’s natural immune defences. Their cancer was also more responsive to treatment.

Combining anti-AXL treatments with cancer treatments may help those treatments work more effectively. Anti-AXL treatments could be part of a treatment plan for aggressive cancers in the future, the researchers say, which “could reduce the primary tumour and metastatic burdens,” potentially helping shrink the cancer and preventing it from spreading to other systems.

Finding a possible therapeutic target that may reduce treatment resistance in HER2+ breast cancer is significant, and Côté says the research team plans to continue this line of inquiry.

This is good news for women diagnosed with HER2+ breast cancer: perhaps in the future, this form of cancer won’t be known for its poor prognosis.

“We hope that this study will lay the groundwork for new effective therapies for HER2+ cancers,” Goyette said.

“We also hope that it will inspire other researchers to examine other unknown aspects of the immune environment of cancers, in order to broaden current knowledge and ultimately improve patients’ chances of survival.”

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