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Centre for Stress and Age-Related Disease
  • What we do
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  • Our research and enterprise projects
    • Our research and enterprise projects
    • A computational protocol to model organophosphonate CWAs and their simulants
    • A reactive oxygen and nitrogen species monitoring system to study their role in cancer
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    • Antibiotic efficacy in treating wound infection
    • Antioxidative enzymes
    • BK channels as Pharmacological targets for therapeutic intervention
    • Clinically reflective cellular model systems for Type 1 diabetes
    • Combating disorders of CNS myelination
    • Controlling infection in urinary catheters
    • C-Stress project
    • Development of a novel platform for local targeted treatment of cardiovascular disease
    • Development of an infection detecting wound dressing
    • Effects of age on signalling and function in the lower bowel
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    • Electrochemical sensor devices to understand ageing and disease mechanisms
    • Exploiting genomics to understand the role of vitamin D in human health and metabolism
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    • organ of Corti
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    • Switchable Molecules: A Radical Approach
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    • The effects of pre-natal alcohol on adolescent learning and memory
    • Translational regulation of stress responses and antibiotic production in Streptomyces bacteria
    • Type 1 Diabetes – cause and cure
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    • Understanding how social isolation increases morbidity and mortality
  • C-Stress project

C-Stress project

Breast cancer is the most common cancer in women. Our goal is to examine the impact of stress hormones, produced from the adrenal gland in response to chronic psychological stress, on disease progression and response to drug treatment. Stress hormones are highly potent and can interact with almost every cell in the body (such as normal, cancer, and immune cells), and we have shown that they can result in damage to DNA leading to cell transformation. A diagnosis of breast cancer is a cause of a great deal of stress, this in itself is significant and more reason for stress management to be considered early on. This project has substantial significance in terms of its potential to further our understanding of enhancing the efficacy of breast cancer pharmacotherapy.

Determining the effects of stress on the efficacy of chemotherapy will suggest the potential utility of pharmacological interventions, and the correct time point in of the disease trajectory at which they should be administered for greatest therapeutic effect. In addition, we will explore new drug delivery methods for drugs to treat breast cancer. Finally, we will also investigate the role of stress on the immune system in breast cancer.

MRM-LHP-breast-cancer

Read the Psychological stress in patients with breast cancer article (pdf) in our Making Research Matter publication.

Project timeframes

This project began in 2014 and is ongoing.

Stress hormones are highly potent and can interact with almost every cell in the body including normal, cancer and immune cells.

Dr Melanie Flint

Project aims

Our overall aim is to determine that psychological interventions will improve the response rates to chemotherapy and, potentially, progression free survival of patients with cancer through the reduction of psychological stress.

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.

Dr Val Jenkins

Project findings and impact

Breast cancer (BC) is the most common cancer in females, affecting one in eight women. We were the first to report that stress hormones (noradrenaline [NA]) at physiological concentrations induce DNA damage and decrease the efficacy of chemotherapy. In research published in BioMed Central, we stated that psychological stress increases the circulating levels of the stress hormones cortisol and norepinephrine (NE) and that chronic exposure to elevated stress hormones has been linked to a reduced response to chemotherapy through induction of DNA damage. We hypothesized that stress hormone signalling may induce DNA damage through the production of reactive oxygen species (ROS)/reactive nitrogen species (RNS) and interference in DNA repair processes, promoting tumourigenesis.

We need to determine the impact of stress reductions in patients with breast cancer, and establish if stress reduction can affect response to chemotherapy. The data from this study will inform a future trial where stress biomarkers and identification of polymorphisms in the Aberrant Drug-Related Behaviours (ADRB) will allow for a personalised medicine approach for the stratification of patients into mindfulness stress responsive/unresponsive groups and those who are unlikely to benefit from β blockers, and determine if stress reductions improve treatment efficacy.

In addition, the research team was awarded a grant from the cancer charity Team Verrico to examine stress hormone receptors in patients with Triple Negative Breast Cancer (TNBC). Triple Negative Breast Cancer (TNBC) accounts for approximately 20 per cent of all subtypes of breast cancer. Patients with TNBC are treated with standard chemotherapy treatments, and these patients exhibit shorter disease-free survival, a higher rate of relapse and can develop resistance to standard therapies.

Through work with women who have recovered from TNBC, the period of most stress was found to be different for each individual; it may be from the moment of suspicion of breast cancer to the diagnosis, or following diagnosis. Patients experience stress for a variety of reasons: through knowledge that they are high risk, enduring multiple biopsies, indirect stress of family members, as well as fear of pain, sickness and potential end of life. Some patients seek stress interventions such as exercise and positive reinforcement from medically-trained individuals. However, each woman stated that stress was a major factor during their cancer history, and that they felt stress could play a role even in tumour progression and treatment. 

Determining the effects of stress on the efficacy of chemotherapy will have an impact on the potential utility of pharmacological interventions such as beta-blockers, or psychological interventions including mindfulness-based stress reduction, and on the correct time point for administration in the disease trajectory for greatest therapeutic effect. The research will impact patients and clinicians, through recognition that stress is a contributing factor for drug resistance in the treatment of breast cancer.

Research team

Dr Melanie S Flint

Dr Greg Scutt

Dr Bhavik Patel

Dr Andrew Overall

Dr Caroline Garrett

Output

Renée L. Flaherty, Matthew Owen, Aidan Fagan-Murphy, Haya Intabli, David Healy, Anika Patel, Marcus C. Allen, Bhavik A. Patel and Melanie S. Flint (2017) Glucocorticoids induce production of reactive oxygen species/reactive nitrogen species and DNA damage through an iNOS mediated pathway in breast cancer. BioMed Central

Reeder, A, Attar, M, Nazario, L, Bathula, C, Zhang, A, Hochbaum, D, Roy, E, Cooper, KL, Oesterreich, S, Davidson NE, Neumann, CA and Flint MS (2015) Stress hormones reduce the efficacy of paclitaxel in triple negative breast cancer through induction of DNA damage, British Journal of Cancer 112 (9) 1461-1470

Funding - Rising Star

Stress modulation of DNA damage and repair in Breast cancer

Partners

Professor Dame Lesley Fallowfield, Professor of Psycho Oncology at the Sussex Health Outcome Research and Education Centre (SHORE-C)

Dr Valerie Shilling (SHORE-C University of Sussex)

Dr Valerie Jenkins (SHORE-C University of Sussex)

Dr Gargi Patel (Sussex Cancer Centre)

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