Many times, cancer patients suffer from a recurrence of the disease after successful treatment. This is because there are undetectable dormant cancer cells in their body that reawakened. Unfortunately, the cancer is often more aggressive the second time around.
Scientists don’t understand what mechanisms are involved in reactivating the cells, but a compelling new study offers a novel hypothesis. The research suggests that an abundance of a particular stress hormone (norepinephrine) can trigger a chain of events that reawakens dormant cancer cells.
The researchers at The Wistar Institute studied mice and analyzed data from 80 patients with lung cancer. They focused on a particular type of immune cell known as polymorphonuclear neutrophils (PMNs), linked to cancer in previous studies – and the hormone norepinephrine. That stress hormone is naturally found in the body, but more is released into the bloodstream when stressed.
The animal experiments involved mice with dormant lung cancer cells in their bodies. The team placed the animals in a confined space, which made them feel trapped and spiked their stress levels. When the mice became stressed, the norepinephrine level rose, which caused neutrophils to release S100A8/A9 proteins and lipids (fatty molecules). Those molecules released by neutrophils were what prompted tumor cells to reawaken.
Lead author Michela Perego, a molecular biologist at the Wistar Institute, said:
“It’s sort of a triangle. And it’s a chain of events that ends up being very powerful in reawakening dormant tumor cells.”
The results hinted that the stress hormones could be targeted using beta-blockers (an already approved drug), potentially helping prevent tumors from returning. So, a subset of the mice was treated with the medication. The dormant tumor cells in those mice didn’t awaken – even though they were equally stressed.
Perego said:
“Beta-blockers are already used in clinics to block norepinephrine for people with heart failure and other stress-sensitive conditions. It’s nice because it’s not a new drug that has to be developed. And it could be something to add to existing cancer therapy to help with patients’ stress hormones.”
Then, the team examined reports on 80 lung cancer patients who had surgery and recovered. Among them, 17 saw their tumors return, and all of them had higher levels of lipids that indicate activated neutrophils (compared with the patients in more prolonged remission).
Perego said:
“We found that patients that experience early cancer relapse have higher stress hormone levels and neutrophil activation markers in their blood compared to patients that do not experience relapse or experience relapse after a long time.”
However, stress alone isn’t responsible for reawakening dormant cancer cells; the entire chain of events needs to happen.
Prego explained in an interview:
“When we say stress, we mean stress hormones, and there are tons of those in the human body. We looked at this specific one, norepinephrine. We all undergo stress, and some handle it better, and some handle it worse. What is very important is that stress alone doesn’t reawaken dormant cells. You need stress hormones, but you also need neutrophils, and you need them to be activated and then for them to produce this specific lipid to turn on tumor cells.
[Therefore], … we think that monitoring stress hormone levels in patients undergoing cancer therapy would be very important in controlling the level of stress hormone to achieve a longer tumor-free time in cancer patients.”
There remain many unanswered questions, like how other stress hormones are related to this mechanism at play. But Perego suggests that, for now, treatments could include monitoring neutrophil activity or stress hormone levels. Eventually, she and her colleagues aim to develop techniques to detect lipids or stress hormones as biomarkers for potential relapse.
