A breakthrough to make it beta: Blocking out stress to treat cancer

Stress is bad, right? It feels bad, and is bad for you. The causes are different for everyone. But how exactly does stress – and nerves – relate to a chronic illness such as cancer?

Monash University’s Associate Professor Erica Sloan, a scientist who specialises in cancer biology and neuro-immunology – how nerves talk to immune cells – began digging into this question 15 years ago, and is now able to say she’s getting much closer to the answers.

Those answers involve all these things – nerves, cells, the immune system, bodily organs, and also the ancient physiological phenomena known as the “fight or flight” response, or stress response.

Humans and mammals evolved to have this response so that when we’re in danger, the brain decides whether to run away or go into battle.

The problem is that the rapid hormonal and physiological changes that come with the stress response (triggered by nerves) can, over time, take a toll on the body.

And, modern Western life is increasingly stressful, for many. The entire mindfulness industry is fuelled by this – humans are too stressed, learn from the Buddhists, be in the moment rather than the past or the future, calm down, breathe. With less stress, the ancients said, comes better health.

Effects of stress on immune cells

Associate Professor Sloan’s background was purely in cancer research. She did her PhD at the Peter MacCallum Cancer Centre until 2003, looking at how cancer spreads. Then she did postdoctoral studies in the US in neuroimmunology, looking at how stress affects immune cells in lymphoid organs such as lymph nodes.

The answer to that enquiry was, yes, immune cells are sensitive to signals from neurotransmitters in the brain, which affects how a virus such HIV gets into those cells.

“There was also some evidence by then that patients with HIV who were very stressed,” she says, “had higher viral loads when they were diagnosed, and didn’t respond as well to viral treatments. But the mechanisms for that were not known.”

“Quantifying stress is challenging. So we’ve focused on how the body receives stress – how it interprets it, and what it does with it.”

With more research came stronger links. This connection between the stress response and the likes of HIV and various cancers became a lot clearer.

“This type of thinking has not historically been widely accepted by Western medicine,” Associate Professor Sloan says. “Eastern medicine has accepted it for a long time. Our goal was to demonstrate the molecular and cellular basis for it, so we can target it with drugs.”

Now, in research that Dr Norman Swan’s Health Report on Radio National called “extraordinary”, Associate Professor Sloan and a team of Monash researchers have discovered that a heart and high blood pressure drug may reduce the spread and growth of breast cancer, and reduce the likelihood of death for breast cancer patients.

The drug is Carvedilol, a beta-blocker. It also blocks stress.

“Beta-blockers are drugs invented in the 1950s that block the heart and cardiovascular system from hearing a stress signal,” she says. “They dampen down the stress response, and stabilise the heart so it can respond in a more measured way.”

The class of drugs are in their third generation; Carvedilol is relatively new. It can be used for heart conditions and blood pressure, but also off-label for stage fright or anxiety.

The key finding – before this work – was that stress acts on cancer cells (as well as HIV) and makes them more able to spread throughout the body. In pre-clinical models, Professor Sloan’s team found the drug stopped this happening, which in turn showed that nerves can affect tumours.

After the pre-clinical studies, the team – with collaborators in Scandinavia – looked at hospital data on women with breast cancer who took the drug, and found they did a lot better in terms of staying alive and keeping the cancer at bay.

They also conducted a clinical trial in Melbourne two years ago with cancer patients and the similar beta-blocker drug Propranolol, which showed equally positive results.

Where to from here?

Now what? Research at the moment is mainly limited to breast cancer, although some work is being done on beta-blockers with pancreatic and blood cancers.

“Based on findings from my lab and others, my feeling is that most cancers that are found in the body will be sensitive to nerves. Brain cancers are a whole different story. It’s a hot topic in cancer research at the moment.”

Read more: What can we learn about chronic disease from COVID-19?

A big scientific hurdle for Associate Professor Sloan, and others studying this potentially life-saving link, is the question of defining stress. Stress levels are different for different people. One person’s high-stress situation might be another person’s “no problem”.

“This is why the field of research hasn’t taken off for such a long time,” she says. “Quantifying stress is challenging. So we’ve focused on how the body receives stress – how it interprets it, and what it does with it. Our work is discovering how cancer cells and immune cells respond to the ‘fight or flight’ signal.”

As cancer patients know only too well, a diagnosis of cancer is inherently stressful.

“How do we acknowledge that?” Professor Sloan asks, “and treat not just the cancer, but also the patient’s wellbeing?”