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

<h3>Background</h3><p dir="ltr">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,...

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التفاصيل البيبلوغرافية
المؤلف الرئيسي: Hadeel Kheraldine (14231609) (author)
مؤلفون آخرون: Ishita Gupta (9203073) (author), Farhan Sachal Cyprian (21633524) (author), Semir Vranic (3353012) (author), Halema F. Al-Farsi (21259523) (author), Maysaloun Merhi (4246147) (author), Said Dermime (79420) (author), Ala-Eddin Al Moustafa (14153205) (author)
منشور في: 2024
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author Hadeel Kheraldine (14231609)
author2 Ishita Gupta (9203073)
Farhan Sachal Cyprian (21633524)
Semir Vranic (3353012)
Halema F. Al-Farsi (21259523)
Maysaloun Merhi (4246147)
Said Dermime (79420)
Ala-Eddin Al Moustafa (14153205)
author2_role author
author
author
author
author
author
author
author_facet Hadeel Kheraldine (14231609)
Ishita Gupta (9203073)
Farhan Sachal Cyprian (21633524)
Semir Vranic (3353012)
Halema F. Al-Farsi (21259523)
Maysaloun Merhi (4246147)
Said Dermime (79420)
Ala-Eddin Al Moustafa (14153205)
author_role author
dc.creator.none.fl_str_mv Hadeel Kheraldine (14231609)
Ishita Gupta (9203073)
Farhan Sachal Cyprian (21633524)
Semir Vranic (3353012)
Halema F. Al-Farsi (21259523)
Maysaloun Merhi (4246147)
Said Dermime (79420)
Ala-Eddin Al Moustafa (14153205)
dc.date.none.fl_str_mv 2024-03-02T03:00:00Z
dc.identifier.none.fl_str_mv 10.1186/s12935-023-03195-z
dc.relation.none.fl_str_mv https://figshare.com/articles/journal_contribution/Targeting_HER2-positive_breast_cancer_cells_by_a_combination_of_dasatinib_and_BMS-202_Insight_into_the_molecular_pathways/29446055
dc.rights.none.fl_str_mv CC BY 4.0
info:eu-repo/semantics/openAccess
dc.subject.none.fl_str_mv Biomedical and clinical sciences
Oncology and carcinogenesis
Pharmacology and pharmaceutical sciences
Dasatinib
PD-1/PD-L1
HER2-positive breast cancer
EMT
Invasion
dc.title.none.fl_str_mv Targeting HER2-positive breast cancer cells by a combination of dasatinib and BMS-202: Insight into the molecular pathways
dc.type.none.fl_str_mv Text
Journal contribution
info:eu-repo/semantics/publishedVersion
text
contribution to journal
description <h3>Background</h3><p dir="ltr">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.</p><h3>Methods</h3><p dir="ltr">Herein, we investigated the impact of DA and PD-L1 inhibitor (BMS-202) combination on HER2-positive breast cancer cell lines, SKBR3 and ZR75.</p><h3>Results</h3><p dir="ltr">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.</p><h3>Conclusion</h3><p dir="ltr">Our findings implicate that a combination of DA and BMS-202 could have a significant impact on the management of HER2-positive breast cancer.</p><h2>Other Information</h2><p dir="ltr">Published in: Cancer Cell International<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1186/s12935-023-03195-z" target="_blank">https://dx.doi.org/10.1186/s12935-023-03195-z</a></p>
eu_rights_str_mv openAccess
id Manara2_002a05321d3080a4cd081b03f82484fd
identifier_str_mv 10.1186/s12935-023-03195-z
network_acronym_str Manara2
network_name_str Manara2
oai_identifier_str oai:figshare.com:article/29446055
publishDate 2024
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spelling Targeting HER2-positive breast cancer cells by a combination of dasatinib and BMS-202: Insight into the molecular pathwaysHadeel Kheraldine (14231609)Ishita Gupta (9203073)Farhan Sachal Cyprian (21633524)Semir Vranic (3353012)Halema F. Al-Farsi (21259523)Maysaloun Merhi (4246147)Said Dermime (79420)Ala-Eddin Al Moustafa (14153205)Biomedical and clinical sciencesOncology and carcinogenesisPharmacology and pharmaceutical sciencesDasatinibPD-1/PD-L1HER2-positive breast cancerEMTInvasion<h3>Background</h3><p dir="ltr">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.</p><h3>Methods</h3><p dir="ltr">Herein, we investigated the impact of DA and PD-L1 inhibitor (BMS-202) combination on HER2-positive breast cancer cell lines, SKBR3 and ZR75.</p><h3>Results</h3><p dir="ltr">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.</p><h3>Conclusion</h3><p dir="ltr">Our findings implicate that a combination of DA and BMS-202 could have a significant impact on the management of HER2-positive breast cancer.</p><h2>Other Information</h2><p dir="ltr">Published in: Cancer Cell International<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1186/s12935-023-03195-z" target="_blank">https://dx.doi.org/10.1186/s12935-023-03195-z</a></p>2024-03-02T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1186/s12935-023-03195-zhttps://figshare.com/articles/journal_contribution/Targeting_HER2-positive_breast_cancer_cells_by_a_combination_of_dasatinib_and_BMS-202_Insight_into_the_molecular_pathways/29446055CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/294460552024-03-02T03:00:00Z
spellingShingle Targeting HER2-positive breast cancer cells by a combination of dasatinib and BMS-202: Insight into the molecular pathways
Hadeel Kheraldine (14231609)
Biomedical and clinical sciences
Oncology and carcinogenesis
Pharmacology and pharmaceutical sciences
Dasatinib
PD-1/PD-L1
HER2-positive breast cancer
EMT
Invasion
status_str publishedVersion
title Targeting HER2-positive breast cancer cells by a combination of dasatinib and BMS-202: Insight into the molecular pathways
title_full Targeting HER2-positive breast cancer cells by a combination of dasatinib and BMS-202: Insight into the molecular pathways
title_fullStr Targeting HER2-positive breast cancer cells by a combination of dasatinib and BMS-202: Insight into the molecular pathways
title_full_unstemmed Targeting HER2-positive breast cancer cells by a combination of dasatinib and BMS-202: Insight into the molecular pathways
title_short Targeting HER2-positive breast cancer cells by a combination of dasatinib and BMS-202: Insight into the molecular pathways
title_sort Targeting HER2-positive breast cancer cells by a combination of dasatinib and BMS-202: Insight into the molecular pathways
topic Biomedical and clinical sciences
Oncology and carcinogenesis
Pharmacology and pharmaceutical sciences
Dasatinib
PD-1/PD-L1
HER2-positive breast cancer
EMT
Invasion