How chronic stress promotes cancer

A cancer diagnosis is some of the most stressful news we can get. I’ve been lucky enough to not have been diagnosed with cancer myself, but I know from our dad’s diagnosis a few years ago just how much of an impact it has on life. Our parents were just getting ready to travel to Sweden for a few weeks. Due to the COVID debacle, they hadn’t been on vacation in a while and were looking forward to enjoying a bit of peace and quiet away from their sons.

Despite minor issues like overweight, high blood pressure, and occasional joint pains, they were both considered overall healthy for their age by modern standards (which, granted, isn’t saying much). The idea of either of them dying soon seemed unreasonable. Dad was in early retirement and mum was soon to join him. Free from their jobs, they’d be free to spend their time travelling and living their best lives for another 30 years. That was the future we expected.

And then dad’s diagnosis struck. Pleural mesothelioma. Not only cancer, but a vicious type at that (1, 2). The doctor told dad that he had 6 to 18 months left if he did nothing. The future we’d been expecting suddenly evaporated and was replaced by fear and uncertainty. Chemotherapy would likely extend his life by a little. And because the cancer was discovered early, surgery was still a viable option. Not knowing what we know today, surgery seemed like his best shot at a longer life, so dad decided to go through with it. Due to the aggressive nature of his cancer, it was still uncertain how much longer he would be with us.

On top of this, no one informed dad about those things he could do to fight cancer himself. He was simply operated on, injected with some chemotherapeutics, and sent home to deal with it on his own. Thanks to our studies in molecular biotech, Merlin and I had enough education to dive into the scientific literature and help him in his fight, eventually developing the Mosaic Method (you can get full guide to it here). This, together with the support of his amazing wife, our mum, significantly lessened the psychological stress of the diagnosis.

But most people aren’t that lucky. Most people are never informed about what they could do, how they themselves could take back some control and many might not have such strong support from their loving family . They are given the diagnosis of unstoppable doom, sent home, and left feeling powerless, stressed, and anxious. You might even have experienced a similar treatment yourself, if you’re a cancer patient.

The worst thing about this is, that the stress caused by the diagnosis can itself worsen patient outcomes (3-6). You may now wonder, how it does that and how you can avoid stress. I’ll tackle how stress helps cancer kill you first and then move on to some strategies of avoiding and resolving stress.

There are two main systems, with which your body responds to stressful situations.

The first is the ‘sympathetic nervous system’ (SNS), the system, which causes the ‘fight-or-flight’ response (7). Its effects are rapid – mediated by adrenaline, among other hormones – and its main purpose is to prepare the body for immediate bodily exertion (7, 8).

The second system is the ‘hypothalamic-pituitary-adrenal axis’ (HPA axis). This system mainly uses cortisol and is slower than the SNS (7). Its main purpose is to adapt the body to prolonged stress (9, 10).

Despite the differences between the two systems, both responses promote adaptation to the demands of a stressful situation. Because of the focus on short term survival, they downregulate processes, which aren’t immediately necessary for survival, including the immune system, proper metabolic regulation, and tissue repair mechanisms (7). Of course, these processes are nonetheless extremely important, particularly in the context of cancer. Metabolic dysregulation is the inciting incident in cancer (11-13), and dysregulated immune system and tissue repair mechanisms directly allow for and promote cancer progression (14-18).

When only exposed to acute stress, this is not a problem, as these functions will only be suppressed for a short while. However, when subjected to chronic stress – a state of prolonged and unresolved stress and anxiety – , these important functions can be suppressed for extended periods of time (7), which is where its danger to cancer comes in.

Chronic activation of the SNS leads to elevated levels of adrenaline. Besides the broadly known systemic effects – like increased heart rate –, adrenaline can also alter the gene expression of cells (19). Gene expression is a major determinant of cell behaviour and is therefore particularly relevant when considering abnormal cell behaviour, as is the case with cancer. In gastric cancer cells, for example, elevated levels of adrenaline have been shown to cause upregulation of genes, which are involved in cell survival and are associated with higher rates of cancer cell growth and metastatic potential (20).

Regarding the immune system, the SNS-mediated stress response is quite interesting. Whilst acute activation can enhance parts of the immune system, prolonged stimulation has the exact opposite effects, weakening the immune response (21). By suppressing the immune response chronic stress thus makes it easier for cancer cells to avoid detection by the immune system, which reduces the death rate of cancer cells and allows for cancer progression (14, 16). In contrast to the SNS, the HPA axis’ response generally suppresses the immune system both during acute and chronic activation (22-24).

Of course, this is just a selection of the effects chronic stress can have, but I think the few examples are enough to illustrate the pattern without being overwhelming. In general, chronic stress promotes cancer progression and aggressiveness, by increasing cancer cell growth rate and decreasing cancer cell death rate (25-28), which is the exact opposite to what we want to achieve. Ideally, we’d want their growth rate to be close to zero and their death rate as high as possible.

Reducing or eliminating chronic stress can help achieve this goal, but doing so is easier said than done.

So, now that we have understood how chronic stress helps cancer kill you, we’ll go over a few actions you can try out to reduce the stress you experience.

The first thing I can recommend is finding a sport you love and doing that sport on a regular basis. It doesn’t really matter what sport it is. It could be swimming, going for runs, bouldering, going to the gym, badminton, soccer, rowing, pilates, hiking, and so on. Whilst sports may stimulate short-term stress responses – especially the one of the SNS –, it lowers long-term activation thus counteracting chronic stress (29-31).

Given the social nature of humans, it shouldn’t come as a surprise, that spending time with loved ones or friends can also reduce stress (32, 33). If you are short on time, this can, of course, be combined with doing sports, especially if you end up loving a team sport. But even if you find bouldering to be what you love, which is a more ‘solitary’ sport, you can still go out with others and socialise during the sessions.

Another important factor contributing to stress is sleep deprivation and sleep quality (34, 35). Engaging in regular and strenuous physical activity can already help improve sleep (36, 37). Beyond that, there are numerous other strategies you can explore—such as reducing blue light exposure before bedtime (38), and getting natural light exposure during the day, especially shortly after waking up (40, 41). That said, prescribing a one-size-fits-all solution isn't particularly useful, as different approaches work for different people. The best advice I can offer is to experiment and stick with whatever methods prove most effective for you.

One last way to reduce stress, that I want to touch on, is to allow yourself to be bored. In the modern world, we seldom simply do nothing. We’re almost always doing something, whether that be working, studying, playing video games, watching movies, scrolling on social media, or something else. Interrupting this stream of constant stimulus gives your brain some time to stray where it wants. I mean, have you ever felt stressed when relaxing on a beach during vacation? I know I haven’t.

Just as with the effects of chronic stress on cancer cells, this list of how to reduce stress is by no means exhaustive. You can probably find fifty more suggestions online on things, which you could try. However, I feel like this post is already long enough and I feel, that trying to provide such a complete list wouldn’t be all that helpful either. What I would recommend is to try some of the things I suggested and see, if they work for you, and then experiment with other things you discover. In the end, it doesn’t matter what works or doesn’t work for me, what matters is what works for you.

Nonetheless, I hope, that I gave you a bit of direction on how you might combat your stress in your fight against cancer.

I wish you a great day and swift healing,

Cedric.

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