07 Mar Beta Blockers May Be Useful Adjuvant For Breast Cancer Through Stress Reduction
MedicalResearch.com Interview with:
Michelle L. Halls
NHMRC Career Development Fellow
Drug Discovery Biology Theme
Monash Institute of Pharmaceutical Sciences
Monash University Parkville Australia
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Halls: Stress causes an increase in the release of hormones including adrenaline. Previous studies have found a link between stress and metastases in triple negative breast cancer. However, what occurs inside a cancer cell in response to adrenaline to drive cancer progression was not known. We have found that adrenaline can directly act on triple negative breast cancer tumour cells via a cell surface receptor called the beta2-adrenoceptor. We identified changes in signalling within the cell that make the tumour cell highly invasive by mapping the signalling pathways that were activated in these cells in response to stress. We found that different signalling pathways converge to amplify the final signal. This ‘positive signalling loop’ was linked to the increased invasion of these cells in response to stress, and was not identified in less aggressive breast cancer cells. This may allow future research to identify new ways to intervene and slow cancer progression. New therapies are important for triple negative breast cancer, as it is particularly aggressive and currently has limited treatment options.
MedicalResearch.com: What should clinicians and patients take away from your report?
Dr. Halls: Recent epidemiological studies have suggested that beta-blockers (drugs that are commonly used to lower blood pressure) may be beneficial to slow disease progression in some forms of breast cancer. However, without understanding how beta-blockers might be working, it hasn’t been clear which patients may benefit. In our study we show that an aggressive breast cancer tumour cell has a cell surface protein called the beta2-adrenoceptor that can bind beta-blockers, but also the stress hormone adrenaline. Activation of the beta2-adrenoceptor on these tumour cells stimulates a ‘positive signalling loop’ to accelerate invasion. The accelerated invasion of these cells was decreased when cells were treated with a beta-blocker. Together with previous research, the current basic research study suggests that beta-blockers may be useful adjuvant therapy for some breast cancers, and provides a mechanism to help explain this link. Future research will determine whether targeting this ‘positive signalling loop’ could be useful in the development of novel therapies.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Dr. Halls: Currently, there are very limited treatment options for triple negative breast cancer. Previous studies have linked increased stress with accelerated onset of metastasis in some forms of breast cancer. This study helps us to start to understand how stress can drive cancer spread by acting on the tumor cells themselves. By understanding how stress accelerates invasion in aggressive breast tumour cells, this work will inform future studies into whether beta-blockers could be a useful adjuvant therapy in the treatment of some aggressive breast cancers.
MedicalResearch.com: Is there anything else you would like to add?
MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.
FASEB J. 2016 Mar;30(3):1144-54. doi: 10.1096/fj.15-277798. Epub 2015 Nov 17.
The β2-adrenoceptor activates a positive cAMP-calcium feedforward loop to drive breast cancer cell invasion.
Pon CK1, Lane JR1, Sloan EK1, Halls ML2.
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Michelle L. Halls (2016). Beta Blockers May Be Useful Adjuvant For Breast Cancer Through Stress Reduction