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
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Publicado: Nature Portfolio 2021
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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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