Beta-adrenergic signaling, a novel target for cancer therapy?

Schüller, Hildegard M.

doi:10.18632/oncotarget.182

Cited by 51 publications

(14 citation statements)

References 30 publications

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“…Because β‐AR stimulation of various cells, such as ECs and cancer cells, can induce cell proliferation through the MAPK pathway (29, 30), we tested whether β‐agonists affect PC and EC proliferation using a BrdU proliferation ELISA assay. β‐Agonists increased PC proliferation in both normal and HG conditions ( Fig.…”

Section: Resultsmentioning

confidence: 99%

β‐Adrenergic receptor agonists attenuate pericyte loss in diabetic retinas through Akt activation

et al. 2017

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Pericytes (PCs) are crucial in maintaining the quiescence of endothelial cells (ECs) and the integrity of EC tight junctions. Especially in diabetic retinopathy (DR), PC loss is one of the early pathologic changes in capillaries of diabetic retinas. Thus, preventing PC loss is beneficial for attenuating vision impairment in patients with DR. Although many studies have revealed the mechanism of PC loss in retinas, little is known about the mechanisms that increase PC survival. We focused on the effect of β-adrenergic receptor agonists (β-agonists) on PC loss in diabetic retinas. In this study, β-agonists increased the cell viability of PCs by increasing PC survival and proliferation. Mechanistically, β-agonist-induced protein kinase B activation in PCs reduced PC apoptosis in response to various stimuli. β2-agonists more potently increased PC survival than β1-agonists. β2-Agonist reduced vascular leakage and PC loss in retinas of mice with streptozotocin-induced diabetes. In cocultures of PCs and ECs, β2-agonists restored the altered permeability and ZO-1 expression in ECs induced by PC loss. We concluded that β-agonists, especially β2-agonists, increase PC survival, thereby preventing diabetes-induced PC loss in retinas. These results provide a potential therapeutic benefit of β-agonists for preventing PC loss in DR.-Yun, J.-H., Jeong, H.-S., Kim, K.-J., Han, M. H., Lee, E. H., Lee, K., Cho, C.-H. β-Adrenergic receptor agonists attenuate pericyte loss in diabetic retinas through Akt activation.

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Section: Resultsmentioning

confidence: 99%

β‐Adrenergic receptor agonists attenuate pericyte loss in diabetic retinas through Akt activation

et al. 2017

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“…In addition, medications that are implicated in the prevention of recurrence may become candidates for use in primary prevention and adjuvant therapy settings. [26,44,46]…”

Section: Discussionmentioning

confidence: 99%

Examining the influence of beta blockers and ACE inhibitors on the risk for breast cancer recurrence: results from the LACE cohort

Ganz

Habel

Weltzien

et al. 2011

Breast Cancer Res Treat

129

159

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There is increasing interest in the relationship between host lifestyle factors and the outcomes of cancer treatment. Behavioral factors, comorbid conditions, and non-cancer related pharmaceutical exposures may affect breast cancer (BC) outcomes. We used observational data from the LACE Study cohort (women with early stage BC from the Kaiser Permanente Northern California Cancer Registry) to examine the association between beta-blockers (BB) and/or angiotensin converting enzyme inhibitors (ACEi) and BC recurrence, BC-specific mortality, and overall mortality. Among 1,779 women, there were 292 BC recurrences, 174 BC deaths, and 323 total deaths. 23% were exposed to either a BB and/or an ACEi. These drugs were associated with older age, postmenopausal status, tamoxifen therapy, greater pre-diagnosis BMI, hypertension, and diabetes. In Cox proportional hazards models, ACEi exposure was associated with BC recurrence (HR 1.56, 95% CI 1.02, 2.39, p=0.04), but not cause-specific mortality or overall mortality. Combined ACEi and BB was associated with overall mortality (HR 1.94, 95% CI 1.22, 3.10, p=0.01). BB exposure was associated with lower hazard of recurrence and cause-specific mortality. However, there was no evidence of a dose response with either medication. For recurrence and cause-specific mortality, BB combined with ACEi was associated with a lower HR for the outcome than when ACEi alone was used. These hypothesis generating findings suggest that BC recurrence and survival were associated with exposure to two commonly used classes of anti-hypertensive medications. These observations need to be confirmed and suggest that greater attention should focus on the potential role of these commonly used medications in BC outcomes.

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“…Beta-adrenergic signalling mediates stress responses, also called "fight or flight", induced by the sympathetic nervous system via catecholamine neurotransmitters represented by adrenaline and noradrenaline. Beta-adrenergic receptors comprising three subtypes (beta-1, beta-2 and beta-3) are constitutively expressed on most mammalian cells, including cancer cells [19]. Their activation can regulate a wide spectrum of cancer-related signalling pathways within both beta-adrenergic receptor expressing cancer cells and other beta-adrenergic receptor expressing cells present in the tumour microenvironment, such as vascular cells and macrophages [20].…”

Section: Discussionmentioning

confidence: 99%

Incidental Use of Beta-Blockers Is Associated with Outcome of Metastatic Colorectal Cancer Patients Treated with Bevacizumab-Based Therapy: A Single-Institution Retrospective Analysis of 514 Patients

Fiala

Ostasov

Šorejs

et al. 2019

Cancers

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Background: Beta-adrenergic signalling plays an important role in several cancer-related processes, including angiogenesis. The impact of beta-blocker use on prognosis of cancer patients treated with antiangiogenic agents is unclear. The aim of this study was to evaluate the association between the incidental use of beta-blockers and the outcomes of patients with metastatic colorectal cancer (mCRC) treated with bevacizumab-based therapy. Methods: Clinical data from 514 mCRC patients treated with bevacizumab between 2005 and 2019 were analysed retrospectively. The association of progression-free survival (PFS) and overall survival (OS) with the incidental use of beta-blockers and other common antihypertensive drugs was assessed. Results: The median PFS and OS for patients using beta-blockers was 11.40 (95% confidence interval (CI) 10.10–13.61) months and 26.8 (95% CI 22.2–32.2) months compared with 8.30 (95% CI 7.80–9.57) and 21.0 (95% CI 17.8–23.8) months for patients not using beta-blockers (p = 0.006 and p = 0.009, respectively). In the Cox multivariate analysis, the use of beta-blockers was a significant factor predicting both PFS (hazard ratio (HR) = 0.763 (95% CI 0.606–0.960), p = 0.021) and OS (HR = 0.730 (95% CI 0.560–0.951), p = 0.020). Conclusions: The results of the present retrospective study suggest that there is a significant association between the use of beta-blockers and favourable outcomes of mCRC patients treated with bevacizumab-based therapy.

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Beta-adrenergic signaling, a novel target for cancer therapy?

Cited by 51 publications

References 30 publications

β‐Adrenergic receptor agonists attenuate pericyte loss in diabetic retinas through Akt activation

β‐Adrenergic receptor agonists attenuate pericyte loss in diabetic retinas through Akt activation

Examining the influence of beta blockers and ACE inhibitors on the risk for breast cancer recurrence: results from the LACE cohort

Incidental Use of Beta-Blockers Is Associated with Outcome of Metastatic Colorectal Cancer Patients Treated with Bevacizumab-Based Therapy: A Single-Institution Retrospective Analysis of 514 Patients

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