Clinical evaluation of BCL-2/XL levels pre- and post- HER2-targeted therapy.

Our previous pre-clinical work defined BCL-2 induction as a critical component of the adaptive response to lapatinib-mediated inhibition of HER2. To determine whether a similar BCL-2 upregulation occurs in lapatinib-treated patients, we evaluated gene expression within tumor biopsies, collected befo...

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Autores principales:	Jason J Zoeller, Michael F Press, Laura M Selfors, Judy Dering, Dennis J Slamon, Sara A Hurvitz, Joan S Brugge
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/403191507d6d430fae491ac157d03afe
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spelling	oai:doaj.org-article:403191507d6d430fae491ac157d03afe2021-11-25T05:54:19ZClinical evaluation of BCL-2/XL levels pre- and post- HER2-targeted therapy.1932-620310.1371/journal.pone.0251163https://doaj.org/article/403191507d6d430fae491ac157d03afe2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0251163https://doaj.org/toc/1932-6203Our previous pre-clinical work defined BCL-2 induction as a critical component of the adaptive response to lapatinib-mediated inhibition of HER2. To determine whether a similar BCL-2 upregulation occurs in lapatinib-treated patients, we evaluated gene expression within tumor biopsies, collected before and after lapatinib or trastuzumab treatment, from the TRIO-B-07 clinical trial (NCT#00769470). We detected BCL2 mRNA upregulation in both HER2+/ER- as well as HER2+/ER+ patient tumors treated with lapatinib or trastuzumab. To address whether mRNA expression correlated with protein expression, we evaluated pre- and post-treatment tumors for BCL-2 via immunohistochemistry. Despite BCL2 mRNA upregulation within HER2+/ER- tumors, BCL-2 protein levels were undetectable in most of the lapatinib- or trastuzumab-treated HER2+/ER- tumors. BCL-2 upregulation was evident within the majority of lapatinib-treated HER2+/ER+ tumors and was often coupled with increased ER expression and decreased proliferation. Comparable BCL-2 upregulation was not observed within the trastuzumab-treated HER2+/ER+ tumors. Together, these results provide clinical validation of the BCL-2 induction associated with the adaptive response to lapatinib and support evaluation of BCL-2 inhibitors within the context of lapatinib and other HER2-targeted receptor tyrosine kinase inhibitors.Jason J ZoellerMichael F PressLaura M SelforsJudy DeringDennis J SlamonSara A HurvitzJoan S BruggePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 5, p e0251163 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jason J Zoeller Michael F Press Laura M Selfors Judy Dering Dennis J Slamon Sara A Hurvitz Joan S Brugge Clinical evaluation of BCL-2/XL levels pre- and post- HER2-targeted therapy.
description	Our previous pre-clinical work defined BCL-2 induction as a critical component of the adaptive response to lapatinib-mediated inhibition of HER2. To determine whether a similar BCL-2 upregulation occurs in lapatinib-treated patients, we evaluated gene expression within tumor biopsies, collected before and after lapatinib or trastuzumab treatment, from the TRIO-B-07 clinical trial (NCT#00769470). We detected BCL2 mRNA upregulation in both HER2+/ER- as well as HER2+/ER+ patient tumors treated with lapatinib or trastuzumab. To address whether mRNA expression correlated with protein expression, we evaluated pre- and post-treatment tumors for BCL-2 via immunohistochemistry. Despite BCL2 mRNA upregulation within HER2+/ER- tumors, BCL-2 protein levels were undetectable in most of the lapatinib- or trastuzumab-treated HER2+/ER- tumors. BCL-2 upregulation was evident within the majority of lapatinib-treated HER2+/ER+ tumors and was often coupled with increased ER expression and decreased proliferation. Comparable BCL-2 upregulation was not observed within the trastuzumab-treated HER2+/ER+ tumors. Together, these results provide clinical validation of the BCL-2 induction associated with the adaptive response to lapatinib and support evaluation of BCL-2 inhibitors within the context of lapatinib and other HER2-targeted receptor tyrosine kinase inhibitors.
format	article
author	Jason J Zoeller Michael F Press Laura M Selfors Judy Dering Dennis J Slamon Sara A Hurvitz Joan S Brugge
author_facet	Jason J Zoeller Michael F Press Laura M Selfors Judy Dering Dennis J Slamon Sara A Hurvitz Joan S Brugge
author_sort	Jason J Zoeller
title	Clinical evaluation of BCL-2/XL levels pre- and post- HER2-targeted therapy.
title_short	Clinical evaluation of BCL-2/XL levels pre- and post- HER2-targeted therapy.
title_full	Clinical evaluation of BCL-2/XL levels pre- and post- HER2-targeted therapy.
title_fullStr	Clinical evaluation of BCL-2/XL levels pre- and post- HER2-targeted therapy.
title_full_unstemmed	Clinical evaluation of BCL-2/XL levels pre- and post- HER2-targeted therapy.
title_sort	clinical evaluation of bcl-2/xl levels pre- and post- her2-targeted therapy.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/403191507d6d430fae491ac157d03afe
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Clinical evaluation of BCL-2/XL levels pre- and post- HER2-targeted therapy.

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