Niche-localized tumor cells are protected from HER2-targeted therapy via upregulation of an anti-apoptotic program in vivo

Drug resistance: Overcoming localized resistance to anti-HER2 therapy Location-specific subpopulations of breast cancer cells adapt to targeted drug treatment, but therapeutic strategies exist to attack these niche-protected cells. A team led by Joan Brugge and Jason Zoeller from Harvard Medical Sch...

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Autores principales:	Jason J. Zoeller, Roderick T. Bronson, Laura M. Selfors, Gordon B. Mills, Joan S. Brugge
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/e1b922c7c04a43b2995e897f3abba5b9
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spelling	oai:doaj.org-article:e1b922c7c04a43b2995e897f3abba5b92021-12-02T11:51:08ZNiche-localized tumor cells are protected from HER2-targeted therapy via upregulation of an anti-apoptotic program in vivo10.1038/s41523-017-0020-z2374-4677https://doaj.org/article/e1b922c7c04a43b2995e897f3abba5b92017-05-01T00:00:00Zhttps://doi.org/10.1038/s41523-017-0020-zhttps://doaj.org/toc/2374-4677Drug resistance: Overcoming localized resistance to anti-HER2 therapy Location-specific subpopulations of breast cancer cells adapt to targeted drug treatment, but therapeutic strategies exist to attack these niche-protected cells. A team led by Joan Brugge and Jason Zoeller from Harvard Medical School, USA, implanted human HER2+ breast tumor cells into the ducts of mouse mammary glands to recapitulate the architecture of ductal carcinoma in situ, a common type of non-invasive breast cancer. They found that cancer cells located on the outer rim of the tumors were resistant to lapatinib, a drug that targets the HER2 protein. Combination treatment with lapatinib and a drug that blocks a pro-survival protein called BCL2 that was specifically enriched in the outer cells after lapatinib treatment helped kill more cells. Complete elimination of the resistant cells was achieved with an antibody-drug conjugate, T-DM1, that binds to HER2 and then releases a chemotherapeutic payload.Jason J. ZoellerRoderick T. BronsonLaura M. SelforsGordon B. MillsJoan S. BruggeNature PortfolioarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Breast Cancer, Vol 3, Iss 1, Pp 1-7 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Jason J. Zoeller Roderick T. Bronson Laura M. Selfors Gordon B. Mills Joan S. Brugge Niche-localized tumor cells are protected from HER2-targeted therapy via upregulation of an anti-apoptotic program in vivo
description	Drug resistance: Overcoming localized resistance to anti-HER2 therapy Location-specific subpopulations of breast cancer cells adapt to targeted drug treatment, but therapeutic strategies exist to attack these niche-protected cells. A team led by Joan Brugge and Jason Zoeller from Harvard Medical School, USA, implanted human HER2+ breast tumor cells into the ducts of mouse mammary glands to recapitulate the architecture of ductal carcinoma in situ, a common type of non-invasive breast cancer. They found that cancer cells located on the outer rim of the tumors were resistant to lapatinib, a drug that targets the HER2 protein. Combination treatment with lapatinib and a drug that blocks a pro-survival protein called BCL2 that was specifically enriched in the outer cells after lapatinib treatment helped kill more cells. Complete elimination of the resistant cells was achieved with an antibody-drug conjugate, T-DM1, that binds to HER2 and then releases a chemotherapeutic payload.
format	article
author	Jason J. Zoeller Roderick T. Bronson Laura M. Selfors Gordon B. Mills Joan S. Brugge
author_facet	Jason J. Zoeller Roderick T. Bronson Laura M. Selfors Gordon B. Mills Joan S. Brugge
author_sort	Jason J. Zoeller
title	Niche-localized tumor cells are protected from HER2-targeted therapy via upregulation of an anti-apoptotic program in vivo
title_short	Niche-localized tumor cells are protected from HER2-targeted therapy via upregulation of an anti-apoptotic program in vivo
title_full	Niche-localized tumor cells are protected from HER2-targeted therapy via upregulation of an anti-apoptotic program in vivo
title_fullStr	Niche-localized tumor cells are protected from HER2-targeted therapy via upregulation of an anti-apoptotic program in vivo
title_full_unstemmed	Niche-localized tumor cells are protected from HER2-targeted therapy via upregulation of an anti-apoptotic program in vivo
title_sort	niche-localized tumor cells are protected from her2-targeted therapy via upregulation of an anti-apoptotic program in vivo
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/e1b922c7c04a43b2995e897f3abba5b9
work_keys_str_mv	AT jasonjzoeller nichelocalizedtumorcellsareprotectedfromher2targetedtherapyviaupregulationofanantiapoptoticprograminvivo AT rodericktbronson nichelocalizedtumorcellsareprotectedfromher2targetedtherapyviaupregulationofanantiapoptoticprograminvivo AT lauramselfors nichelocalizedtumorcellsareprotectedfromher2targetedtherapyviaupregulationofanantiapoptoticprograminvivo AT gordonbmills nichelocalizedtumorcellsareprotectedfromher2targetedtherapyviaupregulationofanantiapoptoticprograminvivo AT joansbrugge nichelocalizedtumorcellsareprotectedfromher2targetedtherapyviaupregulationofanantiapoptoticprograminvivo
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Niche-localized tumor cells are protected from HER2-targeted therapy via upregulation of an anti-apoptotic program in vivo

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