Scientists identify key to preventing metastatic breast cancer

Resistance to breast cancer treatment tied to mutations in estrogen receptor
Resistance to breast cancer treatment tied to mutations in estrogen receptor

Scientists have identified a possible key to preventing secondary cancers in patients with breast cancer, after discovering an enzyme that enhances the spread of the disease. The enzyme lysyl oxidase (LOX) released from the primary tumor causes holes in bone and prepares the bone for the future arrival of cancer cells.

Further, the study found that treatment with a bisphosphonate prevented the changes in the bone and the spread of the disease in mice. Bisphosphonates are an existing class of drugs that prevents the loss of bone mass and is already used to treat diseases such as osteoporosis.

Metastatic breast cancer is the main cause of death from breast cancer. The most common site for the disease to spread is the bone, which occurs in approximately 85% of patients with secondary breast cancer.

The findings suggest that identifying LOX in patients with estrogen-receptor-negative breast cancer early could allow doctors to block the enzyme's activity. That would prevent bone damage and the spread of tumor cells to the bone and halt the progression of the disease.

"This is important progress in the fight against breast cancer metastasis,” said Alison Gartland, PhD, of the University of Sheffield in the United Kingdom. “These findings could lead to new treatments to stop secondary breast tumors growing in the bone, increasing the chances of survival for thousands of patients.”

"We are really excited about our results that show breast cancer tumors send out signals to destroy the bone before cancer cells get there in order to prepare the bone for the cancer cells' arrival.

Garland explained that the next step is to find out exactly how the LOX secreted by the tumor interacts with bone cells. Then, researchers will be able to develop new drugs to stop the formation of the bone lesions and cancer metastasis. She stated that this could also have implications for how other bone diseases are treated, as well.

"Once cancer spreads to the bone it is very difficult to treat. Our research has shed light on the way breast cancer cells prime the bone so it is ready for their arrival,” said study co-leader Janine Erler, PhD, formerly Team Leader in Cancer Biology at The Institute of Cancer Research, London, who now is Associate Professor at the Biotech Research & Innovation Centre (BRIC) at the University of Copenhagen in Denmark.

"If we were able to block this process and translate our work to the clinic, we could stop breast cancer in its tracks, thereby extending patients' lives."

The research, funded by Breast Cancer Campaign, Cancer Research UK, Novo Nordisk Foundation, Danish Cancer Society, Lundbeck Foundation, and both universities, was published in Nature (2015; doi:10.1038/nature14492).
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