Dr Louis Fox: How exercise helps prevent cancer and leads to improved outcomes post-diagnosis

Decades of extensive research has consistently shown that physical activity is good for our health. It is commonly accepted that, relative to our palaeolithic hunter-gatherer ancestors, modern-day humans live comparably (and increasingly) sedentary lifestyles due to our use of modern agriculture, industry, and technology. Whilst these advances have certainly come with many benefits, they have – in the grand scheme of things – happened relatively quickly, meaning that evolutionarily speaking, our genome is still broadly oriented toward tiring out prey with long chases across the savannah; or climbing through dense jungle to find fruit or nuts. We know that modern sedentary behaviour can predispose us to physiological dysfunction and make us vulnerable to disease, but we are still learning much about this complex area. Recently a large body of accumulated research has shifted the paradigm of thinking in a disease area which has historically, and tragically, proven to be one of modern medicine’s most difficult challenges – cancer. Exercise oncology research is showing that exercise can not only be preventative for some cancers; but is also pushing the boundaries of thinking in post-diagnosis oncology care. Can exercise really fight cancer?

First, a necessary caveat. Cancer is not one single disease, but a catch-all term for hundreds of different types of genetic dysregulation in which cells become malignant (broadly speaking: the cells do not die when they are supposed to, evade the immune system, and begin to multiply and invade healthy tissue). So, it’s important to note that all of these different cancers behave differently; some are more vulnerable to certain therapies or interventions than others. Furthermore, every patient differs in terms of their clinical profile and potential response to a given therapy. Scientific findings in the cancer care domain should always be understood through these caveats.

With that said, what does the research show on physical activity? In terms of cancer risk or prevention in the general population, the evidence - while promising - is not as strong as you might think. Although it has been established that obesity can contribute to risk for a few different cancer types, obesity and physical activity are not the same thing. However, the evidence is strong that long-term physical activity behaviour is associated with a lower likelihood of developing a breast or bowel cancer; and the evidence is suggestive that there is a similar relationship for endometrial, lung, oesophageal, and pancreatic cancers, and meningioma. Physical activity associations with cancer risk are notoriously challenging to reliably quantify in non-experimental epidemiological studies, due to methodological issues such as reporting bias from participant self-reporting; reverse causation (did the physical activity prevent the cancer, or the cancer decrease physical activity?); or the presence of competing risks (e.g. inactive individuals in the study sample die of something other than cancer, leading to statistical artifacts that distort the true relationship between physical activity and cancer).

On the other hand, there is now lots of evidence – particularly for breast, bowel, and prostate cancers – showing that engaging with physical activity after a cancer diagnosis can be very beneficial to patients. Exercise has been shown in many studies to improve quality of life and fatigue; and help patients manage side effects of arduous treatment regimens, such as chemotherapy or hormone therapy, by building strength and physical and psychological resilience. For some cancer patients, there is something existentially powerful about taking control of a disorienting and traumatic situation through an exercise regimen. Furthermore, we now have good evidence from epidemiological studies that engaging in physical activity following a diagnosis of certain cancers may actually induce a protective effect on disease progression, helping some patients to stabilise their condition. It may not be a ‘cure’ as such, but this is serious business. How is this possible for a disease that seems to be so characteristically resistant? We don’t yet know fully – but based on what we do know, there are theoretically many ways in which this might occur. The answers, researchers think, may lie in the highly complex ways in which malignant tumours physiologically interface with the rest of the body.

To survive and propagate, malignant tumours have two fundamental requirements: they must evade the immune system; and they must have access to an energy source. Exercise has several effects on the body which could compromise a malignant tumour in one of these ways. At present, there are a great number of physiological and biomolecular mechanisms being speculated upon by researchers in the field, so I will present just a few examples.

Denial of energy. Although this area is not well understood, it has been suggested that exercise may result in the denial of glucose molecules to a malignant tumour, either via redirection to other muscles and organs; or via regulation of metabolic processes that are exploited by malignant tumours for growth.

Mobilisation of immune cells. Exercise increases blood flow and promotes healthy circulation, and it has been shown in animal studies that exercise systemically mobilises key immune cells associated with the removal of problem cells in the body. These immune cells are known as cytotoxic immune cells (or ‘natural killer’ cells). Given that exercise may produce the increased growth and infiltration of veins into a malignant tumour, it is possible that exercise could increase the vulnerability of malignant cells to the body’s natural killer cells.

Drug delivery and tolerance. As noted above, increased vascularisation into the tumour could result in more effective delivery of chemotherapies and immunotherapies. Furthermore, a greater tolerance of side-effects – particularly in the chemotherapy setting – could lead to less people stopping treatment early, and so greater overall toxicity dealt to the tumour.

Disruption to cell signals. It has been speculated, based on existing knowledge, that regulatory ‘cell signalling’ pathways among malignant cells could be disrupted by exercise, potentially via the release of ‘myokines’ – a type of signalling protein that is produced by muscle contractions and implicated in many bodily functions – or some other signalling protein(s). Disruption of these pathways could theoretically slow growth, or even lower the likelihood of metastasis (the spread of a cancer from one anatomical place to another, that often is associated with a much poorer prognosis for the patient).

What is now beyond doubt is that exercise can inflict effects on cancer that are clinically meaningful to patients. As has been stated by leading cancer exercise physiologist Prue Cormie: 

The rhetorical meaning of Cormie’s statement is clear. However, exercise is a behaviour, not a pill. Which means that the therapeutic delivery of this particular remedy – behaviour change – is subject to psychological and social complexity of a slightly different order. Many exercise intervention studies of cancer patients have shown that maintaining patients’ exercise behavioural change in the longer term is challenging. In addition, it is well-accepted beyond the cancer literature that systemic sociodemographic and environmental factors may make it easier for some to change and maintain their exercise behaviour than for others, highlighting a general issue of health equity which is just as relevant to the exercise oncology field as to any other. Then, there are differences in the needs of individuals, and their personalities. How do we begin to address this complexity?

Exercise researchers and physiologists have accepted this challenge armed with the tools of behavioural science. For example, cancer patients at Guy’s and St Thomas’ NHS Foundation Trust can be referred to a year-long exercise programme, utilising a mix of supervised and unsupervised exercise programming, and behaviour change techniques such as goal setting and motivational interviewing, to provide patients with the best chance of adopting and maintaining healthy exercise behaviours. For patients not participating in the programme, research done by our group at Guy’s Hospital and The Royal Marsden Hospital has shown that a brief, 10-minute peer-support intervention delivered systematically (in our case to all prostate cancer patients receiving curative surgery) using patient seminars can – for some patients – increase motivation to engage in exercise; and improve health-related quality of life and fatigue outcomes three months later. Our study showed that in this field, taking a creative approach can sometimes help to subvert systemic barriers to the objective, including sociodemographic inequities. A similar creative philosophy has been used by researchers in Denmark who started a community football team, called Prostate FC, to promote physical activity and peer support among men. These studies have shown that vital peer support and physical activity can potentially be married up to holistically benefit patients.

The field of exercise oncology is reminding us that, much like a high performance sports car languishing in a dark garage too long, the human body is truly in its element when regularly taken for a spin to get its pistons firing. Although we are only just starting to understand this area, it is redefining the way we might think about exercise. Our unfathomably complex bodies are truly capable of remarkable things, and given the right routine and support, it seems that even one of our most formidable medical adversaries can start to feel the burn.