Researchers Discover How Breast Cancer Lurks In The Body, Presenting A New Target For Treating Deadly Recurrent Disease

Breast cancer cells, labeled in green, lie dormant in lung tissue. Once reawakened from this state, the cancer cells are often incredibly aggressive. H. Gao et al./Cell, 2012

Aliyah Kovner 23 May 2018, 23:28

A breakthrough study led by the US National Institutes of Health has identified the mechanism by which breast cancer cells that have migrated away from the original tumor are able to slip into a dormant state, reactivating years to decades later with lethal tenacity.

Writing in Nature Communications, the authors detail how a series of experiments in mice and human cell lines confirmed the long-held suspicion that metastasized breast cancer cells go into an energy-conserving state known as autophagy in response to the stress of colonizing a new part of the body.

And most promisingly, subsequent tests showed that several known autophagy inhibitors greatly reduced the survival of dormant cancer cells, thus paving the way for the development of new treatment methods that may prevent recurrent metastatic breast cancer – a disease that is much more aggressive than primary breast cancer currently estimated to kill 460,000 women worldwide per year.

"Many of the traditional anti-cancer drugs are designed to target dividing cells," co-author Kent Hunter said in a statement.

"Dormant cells, however, are not actively or frequently dividing, and are therefore thought to be resistant to these types of drugs," he added on why it's challenging to treat recurrent breast cancer.

Using a live-mouse model that mimicked metastasis of dormant breast cancer cells to the lungs, the authors first evaluated a chemical autophagy inhibitor, the anti-malarial drug hydroxychloroquine (HCQ). Mice that received HCQ showed 36 times fewer metastatic cells compared with control-treated mice.

Fluorescently tagged images of mouse lung tumor in the group that received control (left), immediate HCQ (middle), and delayed HCQ (right). Below are images of stained histology slides of the same area of the lung seen under a light microscope. Vera-Ramirez et al./Nature Communications, 2018.
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