Although many risk factors have been associated with the progression of cancer, the effects of psychological stress on cancer initiation are only gradually being recognised.
Stress hormones are highly potent and can interact with almost every cell in the body including normal, cancer, and immune cells. Dr Melanie Flint, working at the University of Brighton and, formerly, at the University of Pittsburgh Cancer Institute, has shown that DNA can be damaged as a result of stress, leading to cell transformation. Since this breakthrough research was published, she has been leading further investigations to understand in depth the role that stress can play in patients’ responses to the disease and working towards programmes of treatment that take this into account.
What is the relationship between DNA, cancer cells and stress?
It's important to understand the effects of stress and the role of stress. Exposure to stress produces a physiological response. This involves the activation of the hypothalamic-pituitary axis and the sympathetic nervous system. Mediators of this stress response are the hormones cortisol and catecholamines (adrenaline and noradrenaline), that stimulate the adrenergic pathway. These can produce acute stress or chronic stress depending on how long a person is subject to the source of the stress and, although the body will adapt, prolonged stress can cause hyper-responsiveness to stressors and long-term damage to brain tissues. These chronic stressors might be situations such as caregiving, bereavement, social isolation, the news that a patient may develop cancer, or the process of cancer treatment. As Melanie Flint and her co-researchers state, 'These stressors generally result in an increased and continued release of stress hormones that may favour tumour initiation'.*
The breakthrough in understanding the relationship between DNA, cancer cells and cortisol is likely to bring about further advances in personalised medical interventions that may mitigate some of these problems. By understanding if chronic stress may contribute to cancer it would be possible to widen the offer of stress interventions for patients to help stop the progression of the disease. Melanie Flint’s teams are focused on providing mechanistic evidence for this, with interventions across stress DNA damage, stress and gene changes, and cancer therapies that boost the immune system.
Collaborations develop understanding of link between stress and cancer
The research draws on vital collaborations across the medical profession including General Practitioners and clinicians. Melanie Flint has set up a research network together with the University of Brighton, University of Sussex and Brighton and Sussex Medical School to bring together all researchers in the geographical area working on cancer. The University of Brighton has worked closely with the team at Shore-C, the University of Sussex and Brighton and Sussex Medical School (BSMS), to change awareness of the complex factors associated with the risk of developing cancer and the treatment of cancer. She collaborates with Professor Dame Lesley Fallowfield, Professor of Psycho-Oncology and Dr Val Jenkins, who notes that, “Combining the expertise of laboratory-based scientists with that of psycho-oncologists in an innovative area of research is likely to produce tangible benefits for patients receiving cancer treatments.” National and international interest including liaison with professionals and public from the United States are helping inform the translational engagement.
Most recently, the research team have extended their work into prostate cancer together with Professor Ros Eeles team at the Institute of Cancer Research. Prostate cancer is the most common non-melanoma tumour in men worldwide. In the UK, one in eight men will be affected in their lifetime. Mutations in DNA repair genes are associated with a substantially increased lifetime cancer risk and research has shown that men with mutations and high cortisol and high mean 8-OHdG (a biomarker of oxidative DNA damage) levels have a significantly higher risk of prostate cancer.
How do stress hormones cause breast cancer?
Over many years, under the C-Stress project umbrella, Melanie Flint's laboratory have evolved this research in the field of breast cancer, the most common female cancer, affecting one in seven women. Working with Caroline Garett, Greg Scutt, Andrew Overall as well as students studying towards their PhDs in biomedicine [link with programme area], the research examined the impact of hormones associated with stress in tumour tissue from women with mutations in cancer genes, focusing on women who are at high risk of cancer of the breast. Women with these mutations often develop breast cancer at a younger age and have higher levels of the glucocorticoid hormone cortisol associated with stress. This work was funded by Team Verrico, a charity that supports research into diagnosing responses to cancer diagnosis and cancer treatment and the advance of the education of the general public into cancer development and the experiences of cancer patients.
How does stress affect the spread of cancer?
Melanie Flint and her team are also studying cancer spread. Some patients with advanced cancer of the breast will develop bone/brain cancer metastases which are incurable and highly stressful. The team are examining the mechanisms underpinning this by working with a company Corcept Therapeutics to understand how blocking the glucocorticoid receptor can improve patient outcomes.
Melanie Flint's research into cancer development asks, does stress cause cancer?
Melanie Flint is a Reader in Cancer Research at the University of Brighton with primary research that involves the direct interplay between the hormones cortisol and noradrenaline and the immune and cancer cells. This is accomplished through a mechanistic study of administration of stress hormones to cancerous cells, and observing these effects both in vitro, in vivo and human tissue sample models. The goal of her laboratory is to understand the mechanism through which behavioural stress impacts cancer growth, its initiation, progression and responses to drug treatments.
The abstract to her co-authored paper, 'The role of psychological stress in cancer initiation: clinical relevance and potential molecular mechanisms'* notes that the idea of a physiological response to stress influencing the initiation of cancer is highly controversial. Melanie Flint and her co-authors' research however does recognise a link between initiating stressors, the stress response, and the disease enabling them to propose potential molecular pathways that may link the stress response to early stages of malignant cell transformation.
Melanie Flint has been voted in as a member of the British Breast Group, and the research she leads will continue to impact patients and clinicians, through recognition that stress is a contributing factor for cancer initiation, progression, and metastasis.
* Falcinelli, M, Thaker, PH, Lutgendorf, S, Conzen, S, Flaherty, R & Flint, M 2021, 'The role of psychological stress in cancer initiation: clinical relevance and potential molecular mechanisms', Cancer Research, vol. 81, no. 20, pp. 5131-5140.