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|Authors: ||Antunes Coelho, Marisa Alexandra|
|Internal Tutor: ||COSENTINO, MARCO|
|Co-tutor: ||PEREIRA TEIXEIRA RIBEIRO, LAURA VIRGÍNIA|
|Title: ||Beta-blockers in oncology setting: paving the way for lung cancer|
|Abstract: ||With the growing amount of studies revealing the involvement of β-adrenoceptors (β-AR) in the progression of multiple types of tumours, the hypothesis that β-blockers could be potential candidates for drug repurposing in oncology setting has gaining momentum. In lung cancer, it could be particularly meaningful considering the disappointing results of the current therapeutic approaches.
The compilation of studies disclosed in this thesis intended to investigate the presence β-AR in non-small cell lung cancer (NSCLC) as well as discuss the potential for repurposing β-blockers as a new therapeutic approach for lung cancer. The studies included in this thesis comprise a narrative review, a clinicopathologic study, an in vitro study, and a meta-analysis exploring the effect of β-blockers on overall survival of lung cancer patients and a letter to the editor.
The obtained results suggest that β01 and β2-AR are differently expressed in the histologic subtypes, adenocarcinoma (ADC) and squamous cell carcinoma (SCC). We found that β1-AR expression is present at low levels in both SCC and ADC whereas β2-AR is higher expressed on both histologic subtypes but clearly higher expressed in ADC. The meta-analysis performed, including 7448 patients, showed that lung cancer patients using β-blockers had no increased overall survival when compared to non-users.
Altogether, this work increased the knowledge on the expression pattern of β-AR on NSCLC. Despite the lack of a positive effect of β-blockers on lung cancer overall survival obtained in the meta-analysis, this study should prompt the attention of the scientific community to the fact that there is still a huge margin for improving the concept of β-blockers repurposing in cancer.|
|Keywords: ||β-adrenoceptors; β-blockers, lung cancer, drug repurposing|
|Subject MIUR : ||BIO/14 FARMACOLOGIA|
|Issue Date: ||2018|
|Doctoral course: ||Medicina clinica e sperimentale e Medical Humanities|
|Academic cycle: ||30|
|Publisher: ||Università degli Studi dell'Insubria|
|Other university: ||University of Porto - Portugal - PhD course Experimental and clinical pharmacology and toxicology|
|Citation: ||Antunes Coelho, M.A.Beta-blockers in oncology setting: paving the way for lung cancer (Doctoral Thesis, Università degli Studi dell'Insubria, 2018).|
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