New method to lower breast cancer metastases to brain

Autophagy counteracts brain metastasis in breast cancer and boosts lapatinib.


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Researchers from the University of Arizona Cancer Center found a new way to treat breast cancer that spreads to the brain. By studying the differences between primary breast cancer cells and those in the brain, they discovered that autophagy, a process that helps cancer cells survive, was more active in brain metastases. Blocking this process reduced the cancer’s spread to the brain.

Jennifer Carew, a professor at the university, highlighted the importance of this finding for improving outcomes for patients with brain metastases from breast cancer.

In a study published in Clinical and Translational Medicine, researchers showed that targeting the autophagy gene ATG7 reduced breast cancer brain metastases in mice. To apply this finding to patients, they tested hydroxychloroquine. This FDA-approved drug inhibits autophagy and crosses the blood-brain barrier.

Combining hydroxychloroquine with lapatinib, another breast cancer drug, successfully reduced the number and size of brain metastases in mouse models. Jennifer Carew emphasized the significance of this approach, noting the challenge of treating brain metastases due to the blood-brain barrier.

Hydroxychloroquine has been tested with various anticancer agents before, but this is the first time it’s been studied with lapatinib for breast cancer treatment. The research team, led by Jennifer Carew, was amazed at how effectively this combination reduced brain metastases by targeting a single pathway.

Carew noted that cancer cells are usually tough to stop, so seeing such a significant impact from one change was surprising. Steffan Nawrocki added that since both drugs are FDA-approved, this combination can quickly move to clinical trials for patients with breast cancer brain metastases. Brain metastases are the most common adult central nervous system tumors, affecting 20% to 30% of patients.

The study found a potential way to reduce breast cancer spread to the brain by targeting the autophagy process. Combining the drugs hydroxychloroquine and lapatinib, both FDA-approved, significantly reduced brain metastases in mouse models. This discovery offers hope for more effective treatments for patients with breast cancer brain metastases.

Journal reference:

  1. Steffan T. Nawrocki, Claudia M. Espitia et al., Inhibition of autophagy antagonizes breast cancer brain metastogenesis and augments the anticancer activity of lapatinib. Clinical and Translational Medicine. DOI: 10.1002/ctm2.1662.


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