Inflammation Reactivates Dormant Cancer Cells, Leading to Recurrent Tumors

Recent research sheds light on how inflammation can awaken dormant cancer cells, particularly in cases like breast cancer, leading to cancer recurrence even years after initial treatment. Cancer cells strive to grow and divide, but many enter a state of dormancy when they migrate to distant organs, remaining undetectable and resistant to traditional therapies. This dormant phase allows them to evade treatment and survive in new tissues.

A breakthrough study by researchers at the Whitehead Institute for Biomedical Research, including Robert Weinberg and Jingwei Zhang, investigated what triggers these cells to resume growth. Their findings, published in the Proceedings of the National Academy of Sciences, reveal that inflammation plays a key role. Specifically, tissue inflammation—induced by drugs like bleomycin, a chemotherapy agent used to treat lung conditions—acts as a wake-up call for dormant cancer cells.

The team utilized mouse models implanted with human breast cancer cells, which were engineered to be trackable through fluorescent markers. They observed that inflammation in lung tissue prompted dormant cancer cells to become active, proliferate, and form new tumors. Immune cells called M2 macrophages release signaling molecules known as EGFR ligands, which bind to receptors on dormant cells, activating pathways that stimulate their growth.

Interestingly, once activated, these cancer cells retain a 'memory' of their awakened state, continuing to grow even after inflammatory signals diminish. This suggests a lasting change in their behavior, making relapse difficult to predict and prevent.

Overall, this research emphasizes the importance of understanding the tumor microenvironment and how inflammatory responses can influence cancer progression. While inflammatory signals are essential in initiating reactivation, the detailed mechanisms involved are complex and under ongoing investigation. Better insights into these processes could lead to targeted therapies aimed at preventing metastasis and improving long-term outcomes for cancer patients.

This study underscores the potential of developing treatments that mitigate inflammation or block specific signaling pathways, reducing the risk of cancer cells waking up from dormancy and forming aggressive secondary tumors.