Breast Cancer Cells Exploit Lung's Healing Process to Spread
Researchers at the CU Anschutz Cancer Center have identified a mechanism by which breast cancer cells that spread to the lungs may exploit the body's natural healing processes. This research indicates that cancer cells trigger the lung's normal repair system, inadvertently creating conditions that support tumor growth.
The study was published in Cancer Research Communications.
Key Findings
The research highlights several critical discoveries regarding breast cancer metastasis to the lungs:
- Breast cancer cells can activate the lung's natural healing response.
- Tumors have developed methods to utilize this response to facilitate their expansion.
- An existing anti-inflammatory drug was observed to slow the outgrowth of breast cancer lung metastases in mouse models.
- Data from breast cancer patient samples suggest that targeting these processes could be a promising therapeutic approach.
How Cancer Utilizes the Lung's Healing System
When breast cancer metastasizes to the lungs, it causes damage to the tiny air sacs essential for respiration. Typically, the lung would initiate rapid repair of this damage. Researchers found that cancer cells prolong this damage repair mode, leading to chronic inflammation.
Specialized lung cells, known as alveolar type II cells, which usually aid in rebuilding lung tissue after injury, begin releasing signals that promote tumor growth when cancer cells are present.
Jessica L. Christenson, PhD, first author of the study, noted that cancer cells leverage the lung's inherent repair mechanism.
A Cycle Supporting Tumor Growth
The researchers observed that cancer cells and lung cells engage in reciprocal signaling. Cancer cells activate lung cells, which subsequently release substances that fuel cancer proliferation. This interaction ultimately enables tumors to expand.
Potential Intervention for Metastatic Cancer
The team evaluated roflumilast, a medication approved for treating Chronic Obstructive Pulmonary Disease (COPD). In mouse models of metastatic breast cancer, the drug reduced tumor cell growth and decreased tumor size in the lungs. Roflumilast did not directly kill cancer cells but rather prevented the lung environment from supporting tumor development.
Jennifer K. Richer, PhD, senior author of the study, indicated that this suggests a novel strategy for treating metastatic cancer. Beyond directly targeting cancer cells, it may be possible to target the environment that facilitates their survival and growth.
Significance of the Research
Breast cancer becomes more challenging to treat once it spreads to other parts of the body, frequently metastasizing to the lungs. Approximately one-third of individuals with metastatic breast cancer develop lung metastases, and current treatment options are limited. Given that roflumilast is already an approved medication, its potential application in metastatic cancer may be investigated more rapidly.
Future Research
Researchers intend to study how this drug might function in combination with chemotherapy or immunotherapy and its potential to mitigate common side effects of cancer treatment. They are also exploring inhaled formulations of similar drugs to deliver treatment directly to the lungs.
Jennifer R. Diamond, MD, a collaborator on the project, expressed plans to translate these findings into clinical trials to evaluate roflumilast as a treatment for patients with triple-negative breast cancer, aiming to prevent recurrence in the lungs.