Cold Spring Harbor Laboratory
When you have had cancer, a big worry is whether the cancer will come back – and whether anything you do may change your risk of recurrence. Inflammation is linked with higher risk of cancer recurrence, and our vision is to develop means to prevent recurrence that is caused by inflammation. To do so, we will generate new tools and methods, and focus on the role of one type of inflammatory cell – the neutrophil – in causing cancer recurrence.
Mikala obtained a degree (Ph.D.) in Cancer Biology from the University of Copenhagen, Denmark. She did her dissertation research under the mentorship of Dr. Marja Jäättelä at The Danish Cancer Society. Her postdoctoral training was performed in the laboratory of Dr. Zena Werb at University of California, San Francisco. There, she began developing intravital spinning disk confocal microscopy to understand how the microenvironment influences tumor progression. She came to Cold Spring Harbor Laboratory in 2009 and established a research group that studies how the tumor microenvironment contributes to therapy resistance and metastasis, primarily focusing on the role of inflammatory cells. She received the Department of Defense Breast Cancer Research Program Era of Hope Scholar Award in 2014.
Preventing Metastatic Cancer Recurrence by Targeting Neutrophil Extracellular Traps
Most cancer patients die not from the original tumor, but from cancer that recurs after spreading to a different tissue. For breast cancer patients, cancer may lay dormant for years before it recurs. It has been unclear what leads to recurrence but chronic inflammation and smoking are associated with higher risks. We have now discovered that immune cells called neutrophils can re-awaken dormant cancer by forming so-called “Neutrophil Extracellular Traps” or NETs. Normally, NETs kill bacteria. Neutrophils form NETs by expelling their DNA, which is sticky and traps the bacteria. Bound to the NET-DNA are enzymes that can kill bacteria, but these enzymes can also lead to tissue degradation. NETs are formed during inflammation and smoking and we believe that NETs “re-awaken” the cancer cells by causing tissue degradation.
“The Pershing Square Sohn Prize gives us freedom to take risks and explore new ideas about how inflammation drives cancer recurrence. It is an honor to become part of the Pershing Square Sohn community, and to get resources and relationships needed to ultimately transform our ideas into clinical approaches.”
We will test exactly how the enzymes bound to the NET-DNA re-awaken cancer cells using animal models of dormant breast cancer. We have discovered that lung inflammation via NETs can help cancer spread to the bones and we will determine how that happens. We have also found that smoking stimulates neutrophils to form NETs and we will test if this may explain why cancer patients that smoke have twice the risk of recurrence compared to patients that do not.
“To me, innovation in research is using knowledge, unexpected findings, and imagination to make technological and conceptional leaps. It requires the ability to take risks and to focus on important questions.”
Our experimental data suggest that targeting NETs could be a new way to prevent cancer from recurring. Our ultimate goal is therefore to devise approaches to target NETs to prevent cancer from recurring while still allowing NETs to kill bacteria.