ORCID Profile
0000-0003-0769-516X
Current Organisation
Monash University
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Publisher: American Association for the Advancement of Science (AAAS)
Date: 26-04-2023
DOI: 10.1126/SCITRANSLMED.ADF1147
Abstract: Beta-adrenergic blockade has been associated with improved cancer survival in patients with triple-negative breast cancer (TNBC), but the mechanisms of these effects remain unclear. In clinical epidemiological analyses, we identified a relationship between beta-blocker use and anthracycline chemotherapy in protecting against TNBC progression, disease recurrence, and mortality. We recapitulated the effect of beta-blockade on anthracycline efficacy in xenograft mouse models of TNBC. In metastatic 4T1.2 and MDA-MB-231 mouse models of TNBC, beta-blockade improved the efficacy of the anthracycline doxorubicin by reducing metastatic development. We found that anthracycline chemotherapy alone, in the absence of beta-blockade, increased sympathetic nerve fiber activity and norepinephrine concentration in mammary tumors through the induction of nerve growth factor (NGF) by tumor cells. Moreover, using preclinical models and clinical s les, we found that anthracycline chemotherapy up-regulated β 2 -adrenoceptor expression and lified receptor signaling in tumor cells. Neurotoxin inhibition of sympathetic neural signaling in mammary tumors using 6-hydroxydopamine or genetic deletion of NGF or β 2 -adrenoceptor in tumor cells enhanced the therapeutic effect of anthracycline chemotherapy by reducing metastasis in xenograft mouse models. These findings reveal a neuromodulatory effect of anthracycline chemotherapy that undermines its potential therapeutic impact, which can be overcome by inhibiting β 2 -adrenergic signaling in the tumor microenvironment. Supplementing anthracycline chemotherapy with adjunctive β 2 -adrenergic antagonists represents a potential therapeutic strategy for enhancing the clinical management of TNBC.
Publisher: Elsevier BV
Date: 04-2021
Publisher: MDPI AG
Date: 17-07-2015
Publisher: Public Library of Science (PLoS)
Date: 10-12-2018
Publisher: Elsevier BV
Date: 08-2018
Publisher: Springer Science and Business Media LLC
Date: 20-06-2022
DOI: 10.1038/S41416-022-01891-7
Abstract: The association between use of β-blockers and breast cancer (BC) prognosis has been investigated in several observational studies, with conflicting results. We performed a nationwide cohort study and a meta-analysis to investigate the association, and assess if it varied between molecular subtypes of BC. We identified women aged ≥50 years with BC diagnosed between 2004 and 2018 in Norway. We used Cox regression models to estimate the association between β-blocker use at diagnosis and BC-specific survival, overall and by molecular subtype. We performed a meta-analysis of observational studies that reported molecular subtype-specific estimates of this association. We included 30,060 women, of which 4461 (15%) used β-blockers. After a median follow-up of 5.1 years, 2826 (9%) died of BC. Overall, β-blocker use was not associated with BC-specific survival (hazard ratio [HR] = 1.07 95% confidence interval [CI]: 0.97–1.19). We found an association only in triple-negative BC (TNBC) patients (HR = 0.66 95% CI: 0.47–0.91). This was confirmed in the meta-analysis: β-blocker use was associated with progression/recurrence-free (HR = 0.58 95% CI: 0.38–0.89) and BC-specific survival (HR = 0.74 95% CI: 0.55–1.00) in TNBC patients only. In our cohort of BC patients and in the meta-analysis, β-blocker use was associated with prolonged BC-specific survival only in TNBC patients.
Publisher: Elsevier BV
Date: 10-2016
Publisher: Elsevier BV
Date: 05-2022
Publisher: SAGE Publications
Date: 2022
DOI: 10.1177/15347354221096081
Abstract: The relationship between psychosocial factors and cancer has intrigued people for centuries. In the last several decades there has been an expansion of mechanistic research that has revealed insights regarding how stress activates neuroendocrine stress-response systems to impact cancer progression. Here, we review emerging mechanistic findings on key pathways implicated in the effect of stress on cancer progression, including the cellular immune response, inflammation, angiogenesis, and metastasis, with a primary focus on the mediating role of the sympathetic nervous system. We discuss converging findings from preclinical and clinical cancer research that describe these pathways and research that reveals how these stress pathways may be targeted via pharmacological and mind-body based interventions. While further research is required, the body of work reviewed here highlights the need for and feasibility of an integrated approach to target stress pathways in cancer patients to achieve comprehensive cancer treatment.
No related grants have been discovered for Aeson Chang.