Evaluation of the treatment strategies on patient-derived xenograft mice of human breast tumor

Copyright © 2020 Elsevier B.V. All rights reserved..

Since only a minority of patients may respond to single-agent therapies, methods to test the potential antitumor activity of rational combination therapies are still needed. This study aimed to characterize the efficacy of antitumor combination therapies in vivo within the primary tumor using patient-derived xenograft (PDX) models by gamma-irradiation-induced immune suppression. We employed four Luminal A PDX models obtained from human mammary tumors grown in mice. PDX models were implanted into the right flank of mice, and treatments have ensued once tumor volume reached ~150 mm3. Four of the active drugs- Adriamycin, Cyclophosphamide, Taxotere, and Tamoxifen-were tested in vivo to treat mammary tumors. The tumor volume was measured during the study. The mice's immune system was inherently suppressed by gamma irradiation, thus allowing human tumors to grow. The results showed that the tumorigenesis rate of the PDX model was from 65 to 80%. PDX models were successfully established with a high frequency of tumor engraftment. Humanized mice treated with a two-drug regimen, that is, adriamycin + cyclophosphamide exhibited an increased antitumor response than a three-drug regimen, that is, adriamycin + cyclophosphamide + taxotere that correlated with tumor growth inhibition. Combination therapies with adriamycin + cyclophosphamide in PDX mice reduced tumor growth in four Luminal A PDX models. These preclinical results suggest that a two-drug regimen than a three-drug regimen can be useful for breast cancer patients. This study provides insights for future studies combining chemotherapeutics with targeted therapies using PDX models by gamma-irradiation-induced immune suppression.

Errataetall:

RetractionIn: Eur J Pharmacol. 2024 Apr 15;969:176350. - PMID 38458940

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:889

Enthalten in:

European journal of pharmacology - 889(2020) vom: 15. Dez., Seite 173605

Sprache:

Englisch

Beteiligte Personen:

Khalighfard, Solmaz [VerfasserIn]
Alizadeh, Ali Mohammad [VerfasserIn]
Poorkhani, Amirhoushang [VerfasserIn]
Motahari, Mohammadmehdi [VerfasserIn]
Tahmasebifar, Arash [VerfasserIn]
Omranipour, Ramesh [VerfasserIn]
Keshavarz, Pedram [VerfasserIn]
Haddad, Peiman [VerfasserIn]

Links:

Volltext

Themen:

Antineoplastic Agents
Breast cancer
Chemotherapy
Journal Article
Mice
Patient-derived xenograft
Pre-clinical
Retracted Publication

Anmerkungen:

Date Completed 14.05.2021

Date Revised 21.03.2024

published: Print-Electronic

RetractionIn: Eur J Pharmacol. 2024 Apr 15;969:176350. - PMID 38458940

Citation Status MEDLINE

doi:

10.1016/j.ejphar.2020.173605

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM31551065X