Researchers at the CU Anschutz Cancer Center have discovered how breast cancer cells that spread to the lungs may take advantage of the body’s natural healing response and how a commonly used drug might slow that process. They found that breast cancer cells that spread to the lungs trigger the lung’s normal repair system, creating conditions that unintentionally help tumors grow.
The study was published this month in Cancer Research Communications.
Key Findings
How Cancer Uses the Lung’s Healing System
When breast cancer spreads to the lungs, it damages tiny air sacs needed for people to breathe. Normally the lung would quickly work to repair this damage.
Researchers found that cancer cells prolong the damage repair mode leading to chronic inflammation.
Specialized lung cells called alveolar type II cells normally help rebuild lung tissue after injury. When cancer cells are present, these lung cells begin releasing signals that encourage tumors to grow.
“The lung is doing what it is designed to do and that is to clear debris and repair damage,” said Jessica L. Christenson, PhD , first author of the study and an instructor in the Department of Pathology at CU Anschutz. “But in this case, cancer cells are taking advantage of that repair response.”
A Cycle That Helps Tumors Grow
The researchers found that cancer cells and lung cells begin signaling to each other.
Cancer cells activate lung cells which then release substances that fuel cancer growth. This eventually allows tumors to expand.
A Possible New Way to Slow Metastatic Cancer
The team tested Roflumilast, a medication approved to treat Chronic Obstructive Pulmonary Disease (COPD).
In mouse models of metastatic breast cancer, the drug slowed tumor cell growth and reduced the size of tumors in the lungs. Rather than killing cancer cells, the drug prevented the lung environment from helping the tumors grow.
“This suggests a new strategy for treating metastatic cancer,” said Jennifer K. Richer, PhD , senior author of the study and professor of pathology at the CU Anschutz Cancer Center. “In addition to targeting cancer cells themselves, we may also be able to target the environment that allows them to thrive.”
Why This Matters
Breast cancer is more difficult to treat once it spreads to other parts of the body. It often spreads to the lungs.
About one third of people with metastatic breast cancer develop lung metastases and treatment options are limited.
Because roflumilast is already approved for another condition, it may be possible to study its potential use in metastatic cancer more quickly.
What Comes Next
Researchers plan to study how this drug might work together with chemotherapy or immunotherapy and whether it can effectively alleviate common side effects of cancer treatment. They are also exploring inhaled versions of similar drugs that could deliver treatment directly to the lungs.
“We are very excited to translate these findings to the clinic and evaluate roflumilast as a treatment for patients with triple-negative breast cancer to prevent recurrence in the lungs,” said Jennifer R. Diamond, MD , a professor of medical oncology and medical director of the Cancer Clinical Trials Office (CCTO) at the CU Anschutz Cancer Center and close collaborator on this project.
The study was supported by the National Institutes of Health, University of Colorado Cancer Center, American Cancer Society and METAvivor.
About the University of Colorado Anschutz
The University of Colorado Anschutz is a world-class academic medical campus leading transformative advances in science, medicine, education and patient care. The campus includes the University of Colorado’s health professional schools, more than 60 centers and institutes, and two nationally ranked independent hospitals - UCHealth University of Colorado Hospital and Children's Hospital Colorado - which see nearly three million adult and pediatric patient visits each year. Innovative, interconnected and highly collaborative, CU Anschutz delivers life-changing treatments, exceptional patient care and top-tier professional training. The campus conducts world-renowned research supported by $890 million in funding, including $762 million in sponsored awards and $128 million in philanthropic gifts for research.
Cancer Research Communications