Research reveals possible method to lower breast cancer brain metastases

Researchers at the University of Arizona Cancer Center at UArizona Health Sciences have discovered a promising biological mechanism that could lead to more effective treatments for breast cancer that has spread to the brain. Through their study, they identified significant metabolic differences between primary breast cancer cells and those that metastasize to the brain, specifically noting an increase in autophagy in brain metastases. Autophagy is a cellular recycling process that allows cancer cells to survive under stressful conditions, such as those induced by anticancer drugs.

"The prognosis for individuals with brain metastases from breast cancer is extremely unfavorable, and the management of breast cancer metastases in the brain remains a formidable challenge," stated senior author Jennifer Carew, PhD. The researchers were able to impede the formation of brain metastases in breast cancer cells by disrupting the autophagy pathway.

Published in Clinical and Translational Medicine, the study initially demonstrated that targeting the key autophagy-regulating gene ATG7 significantly reduced the ability of breast cancer cells to form brain metastases in mouse models.

To translate these findings into potential treatments, the research team explored the use of hydroxychloroquine, a drug approved by the Food and Drug Administration (FDA), for treating breast cancer brain metastases. Hydroxychloroquine inhibits autophagy at a later stage and can cross the blood-brain barrier, an obstacle that most drugs cannot efficiently overcome. This makes it a promising candidate for treating brain metastases.

"Most drugs do not efficiently cross the blood-brain barrier, and that is one of the key reasons why brain metastases are so difficult to treat," explained Carew, a professor of medicine at the UArizona College of Medicine—Tucson and a member of the UArizona Cancer Center Clinical and Translational Oncology Program.

The research team combined hydroxychloroquine with lapatinib, another FDA-approved drug for treating breast cancer. They found that this combination successfully reduced the number and size of breast cancer brain metastases in mouse models. While hydroxychloroquine has been tested with other anticancer agents in early-phase clinical trials, this is the first instance of its combination with lapatinib being studied for breast cancer therapy.

Carew expressed her amazement at how effectively they were able to reduce the ability of breast cancer cells to form brain metastases by targeting a single pathway. "Cancer cells, unfortunately, have evolved so many ways that make it difficult for us to stop their growth or kill them," she said. "It is always somewhat surprising when you see how changing only one thing can have an impact."

First author Steffan Nawrocki, PhD, co-director of the Cancer Center Clinical and Translational Oncology Program and professor at the UArizona College of Medicine—Tucson, added, "Our group and others have shown that activation of autophagy makes it harder for many different types of cancer therapies to kill cancer cells and this promotes drug resistance. Because hydroxychloroquine and lapatinib are already FDA approved, we can advance this drug combination quickly into a clinical trial for patients with breast cancer brain metastases."

Brain metastases are the most common adult central nervous system tumors, with 20% to 30% of cases originating from breast cancer patients, particularly those with triple-negative and HER2 amplified disease. The prognosis remains poor, with only 20% of patients surviving beyond five years.

The study also involved contributions from co-authors Wei Wang, PhD, Trace M. Jones, PhD, Claudia M. Espitia, Maria Janina Carrera Espinoza, PhD, Madison E. Gamble, Sruthi Sureshkumar, and Mengyang Chang. The research received support from the National Cancer Institute, a division of the National Institutes of Health, under various award numbers.

This significant breakthrough opens new avenues for treating brain metastases in breast cancer patients, potentially improving their survival rates and quality of life.

How to obtain the latest research advancements in the field of biopharmaceuticals?

In the Synapse database, you can keep abreast of the latest research and development advances in drugs, targets, indications, organizations, etc., anywhere and anytime, on a daily or weekly basis. Click on the image below to embark on a brand new journey of drug discovery!