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Cancer Cell International
Published in: Cancer Cell International 1/2024

Open Access 01-12-2024 | Dasatinib | Research

Targeting HER2-positive breast cancer cells by a combination of dasatinib and BMS-202: Insight into the molecular pathways

Authors: Hadeel Kheraldine, Ishita Gupta, Farhan Sachal Cyprian, Semir Vranic, Halema F. Al-Farsi, Maysaloun Merhi, Said Dermime, Ala-Eddin Al Moustafa

Published in: Cancer Cell International | Issue 1/2024

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Abstract

Background

Recent investigations have reported the benefits of using a tyrosine kinase inhibitor, dasatinib (DA), as well as programmed death-ligand 1 (PD-L1) inhibitors in the management of several solid tumors, including breast cancer. Nevertheless, the outcome of the combination of these inhibitors on HER2-positive breast cancer is not explored yet.

Methods

Herein, we investigated the impact of DA and PD-L1 inhibitor (BMS-202) combination on HER2-positive breast cancer cell lines, SKBR3 and ZR75.

Results

Our data reveal that the combination significantly inhibits cell viability of both cancer cell lines as compared to monotreatment. Moreover, the combination inhibits epithelial-mesenchymal transition (EMT) progression and reduces cancer cell invasion by restoring E-cadherin and β-catenin expressions and loss of vimentin, major biomarkers of EMT. Additionally, the combination reduces the colony formation of both cell lines in comparison with their matched control. Also, the combination considerably inhibits the angiogenesis of the chorioallantoic membrane model compared with monotreatment. Molecular pathway analysis of treated cells shows that this combination blocks HER2, AKT, β-catenin, and JNK1/2/3 activities.

Conclusion

Our findings implicate that a combination of DA and BMS-202 could have a significant impact on the management of HER2-positive breast cancer.
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Metadata
Title
Targeting HER2-positive breast cancer cells by a combination of dasatinib and BMS-202: Insight into the molecular pathways
Authors
Hadeel Kheraldine
Ishita Gupta
Farhan Sachal Cyprian
Semir Vranic
Halema F. Al-Farsi
Maysaloun Merhi
Said Dermime
Ala-Eddin Al Moustafa
Publication date
01-12-2024
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2024
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-023-03195-z

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Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

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Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
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