Activity of docetaxel, carboplatin, and doxorubicin in patient-derived triple-negative breast cancer xenografts

Abstract Triple-negative breast cancer (TNBC) is highly responsive to neoadjuvant polychemotherapy regimens including anthracyclines, taxanes, and, more recently, carboplatin. However, there is inadequate information on the individual contribution of each of these agents to the global activity of th...

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Autores principales:	Miguel Martin, Rocio Ramos-Medina, Rebeca Bernat, Jose Angel García-Saenz, Maria del Monte-Millan, Enrique Alvarez, Maria Cebollero, Fernando Moreno, Eva Gonzalez-Haba, Oscar Bueno, Paula Romero, Tatiana Massarrah, Isabel Echavarria, Yolanda Jerez, Blanca Herrero, Ricardo Gonzalez del Val, Nerea Lobato, Patricia Rincon, Maria Isabel Palomero, Ivan Marquez-Rodas, Santiago Lizarraga, Fernando Asensio, Sara Lopez-Tarruella
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6320cb09619d46bdb0b5fd843bc4c5e3
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spelling	oai:doaj.org-article:6320cb09619d46bdb0b5fd843bc4c5e32021-12-02T14:25:21ZActivity of docetaxel, carboplatin, and doxorubicin in patient-derived triple-negative breast cancer xenografts10.1038/s41598-021-85962-42045-2322https://doaj.org/article/6320cb09619d46bdb0b5fd843bc4c5e32021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-85962-4https://doaj.org/toc/2045-2322Abstract Triple-negative breast cancer (TNBC) is highly responsive to neoadjuvant polychemotherapy regimens including anthracyclines, taxanes, and, more recently, carboplatin. However, there is inadequate information on the individual contribution of each of these agents to the global activity of the combinations, and the use of combinations of up to four of these drugs is associated with relevant toxicity. Identifying single-drug activity in the clinical neoadjuvant setting is challenging. We developed patient-derived xenografts (PDXs) from several chemotherapy-naïve TNBC samples to assess the antitumor activity of single drugs and combinations of drugs. PDXs were established from chemotherapy-naïve TNBC samples. Nine TNBC PDX models (all of which corresponded to a basal-like phenotype according to the PAM50 classifier) were treated with carboplatin, docetaxel, and doxorubicin and the combination of docetaxel and carboplatin. Only one of nine PDX models showed sensitivity to doxorubicin, while eight of nine PDX models showed sensitivity to docetaxel and carboplatin as single agents. The 3 PDX models derived from patients with gBRCA-1 or gPALB2 mutations were very sensitive to carboplatin single agent. All 6 PDX models from patients without hereditary germ-line mutations showed increased sensitivity to the combination of docetaxel and carboplatin. In the present study, docetaxel and carboplatin single agents were active drugs against basal-like TNBC, while doxorubicin monotherapy showed low activity. The combination of docetaxel and carboplatin was more effective than the drugs used as single agents, except in the PDX from patients with gBRCA1/PALB2 mutations.Miguel MartinRocio Ramos-MedinaRebeca BernatJose Angel García-SaenzMaria del Monte-MillanEnrique AlvarezMaria CebolleroFernando MorenoEva Gonzalez-HabaOscar BuenoPaula RomeroTatiana MassarrahIsabel EchavarriaYolanda JerezBlanca HerreroRicardo Gonzalez del ValNerea LobatoPatricia RinconMaria Isabel PalomeroIvan Marquez-RodasSantiago LizarragaFernando AsensioSara Lopez-TarruellaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Miguel Martin Rocio Ramos-Medina Rebeca Bernat Jose Angel García-Saenz Maria del Monte-Millan Enrique Alvarez Maria Cebollero Fernando Moreno Eva Gonzalez-Haba Oscar Bueno Paula Romero Tatiana Massarrah Isabel Echavarria Yolanda Jerez Blanca Herrero Ricardo Gonzalez del Val Nerea Lobato Patricia Rincon Maria Isabel Palomero Ivan Marquez-Rodas Santiago Lizarraga Fernando Asensio Sara Lopez-Tarruella Activity of docetaxel, carboplatin, and doxorubicin in patient-derived triple-negative breast cancer xenografts
description	Abstract Triple-negative breast cancer (TNBC) is highly responsive to neoadjuvant polychemotherapy regimens including anthracyclines, taxanes, and, more recently, carboplatin. However, there is inadequate information on the individual contribution of each of these agents to the global activity of the combinations, and the use of combinations of up to four of these drugs is associated with relevant toxicity. Identifying single-drug activity in the clinical neoadjuvant setting is challenging. We developed patient-derived xenografts (PDXs) from several chemotherapy-naïve TNBC samples to assess the antitumor activity of single drugs and combinations of drugs. PDXs were established from chemotherapy-naïve TNBC samples. Nine TNBC PDX models (all of which corresponded to a basal-like phenotype according to the PAM50 classifier) were treated with carboplatin, docetaxel, and doxorubicin and the combination of docetaxel and carboplatin. Only one of nine PDX models showed sensitivity to doxorubicin, while eight of nine PDX models showed sensitivity to docetaxel and carboplatin as single agents. The 3 PDX models derived from patients with gBRCA-1 or gPALB2 mutations were very sensitive to carboplatin single agent. All 6 PDX models from patients without hereditary germ-line mutations showed increased sensitivity to the combination of docetaxel and carboplatin. In the present study, docetaxel and carboplatin single agents were active drugs against basal-like TNBC, while doxorubicin monotherapy showed low activity. The combination of docetaxel and carboplatin was more effective than the drugs used as single agents, except in the PDX from patients with gBRCA1/PALB2 mutations.
format	article
author	Miguel Martin Rocio Ramos-Medina Rebeca Bernat Jose Angel García-Saenz Maria del Monte-Millan Enrique Alvarez Maria Cebollero Fernando Moreno Eva Gonzalez-Haba Oscar Bueno Paula Romero Tatiana Massarrah Isabel Echavarria Yolanda Jerez Blanca Herrero Ricardo Gonzalez del Val Nerea Lobato Patricia Rincon Maria Isabel Palomero Ivan Marquez-Rodas Santiago Lizarraga Fernando Asensio Sara Lopez-Tarruella
author_facet	Miguel Martin Rocio Ramos-Medina Rebeca Bernat Jose Angel García-Saenz Maria del Monte-Millan Enrique Alvarez Maria Cebollero Fernando Moreno Eva Gonzalez-Haba Oscar Bueno Paula Romero Tatiana Massarrah Isabel Echavarria Yolanda Jerez Blanca Herrero Ricardo Gonzalez del Val Nerea Lobato Patricia Rincon Maria Isabel Palomero Ivan Marquez-Rodas Santiago Lizarraga Fernando Asensio Sara Lopez-Tarruella
author_sort	Miguel Martin
title	Activity of docetaxel, carboplatin, and doxorubicin in patient-derived triple-negative breast cancer xenografts
title_short	Activity of docetaxel, carboplatin, and doxorubicin in patient-derived triple-negative breast cancer xenografts
title_full	Activity of docetaxel, carboplatin, and doxorubicin in patient-derived triple-negative breast cancer xenografts
title_fullStr	Activity of docetaxel, carboplatin, and doxorubicin in patient-derived triple-negative breast cancer xenografts
title_full_unstemmed	Activity of docetaxel, carboplatin, and doxorubicin in patient-derived triple-negative breast cancer xenografts
title_sort	activity of docetaxel, carboplatin, and doxorubicin in patient-derived triple-negative breast cancer xenografts
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/6320cb09619d46bdb0b5fd843bc4c5e3
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Activity of docetaxel, carboplatin, and doxorubicin in patient-derived triple-negative breast cancer xenografts

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