Pharmacodynamic modelling reveals synergistic interaction between docetaxel and SCO-101 in a docetaxel-resistant triple negative breast cancer cell line.
Antineoplastic Agents
/ pharmacology
Antineoplastic Combined Chemotherapy Protocols
/ pharmacology
Apoptosis
/ drug effects
Cell Line, Tumor
Cell Proliferation
/ drug effects
Cell Survival
/ drug effects
Docetaxel
/ pharmacology
Drug Interactions
Drug Synergism
Female
Humans
Triple Negative Breast Neoplasms
/ drug therapy
Cancer research
Combination therapy
Drug–drug interactions
PK-PD modelling
Preclinical development
Journal
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
ISSN: 1879-0720
Titre abrégé: Eur J Pharm Sci
Pays: Netherlands
ID NLM: 9317982
Informations de publication
Date de publication:
30 May 2020
30 May 2020
Historique:
received:
02
12
2019
revised:
23
02
2020
accepted:
17
03
2020
pubmed:
24
3
2020
medline:
5
1
2021
entrez:
24
3
2020
Statut:
ppublish
Résumé
One of the primary barriers in treating cancer patients is the development of resistance to the available treatments. This is the case for treatment of triple negative breast cancer (TNBC) with docetaxel, which is part of the neoadjuvant treatment for TNBC. The novel compound SCO-101 is under investigation for its potential treatment effect in several types of drug resistant cancer. The aim of this study was to establish a pharmacodynamic model that captures the effect of docetaxel, SCO-101, and the combination on cell survival in docetaxel resistant MDA-MB-231 TNBC cells. Several combination models were compared and a recently published combination model, the general pharmacodynamic interaction model (GPDI), provided the best fit. The model allowed for description and quantification of the interaction between docetaxel and SCO-101 with respects to both maximal effect and potency. Based on this model, SCO-101 has a synergistic effect with docetaxel. This synergy is not present in the maximal effect, but the combination of SCO-101 and docetaxel showed an approximately 60% increase in potency compared to docetaxel alone. Furthermore, the predicted model surface for the combination provided key information regarding promising dose ratios and dose levels for further studies of the combination. Lastly, the study presents a use case for the GPDI model, which provides a way to quantify and interpret drug-drug interactions.
Identifiants
pubmed: 32201343
pii: S0928-0987(20)30104-4
doi: 10.1016/j.ejps.2020.105315
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
Docetaxel
15H5577CQD
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
105315Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest Asbjørn Nøhr-Nielsen was funded by Novo Nordisk A/S. Novo Nordisk A/S had no role in the design or conduct of the study, collection, management, analysis, or interpretation of data or in preparation of the manuscript. Nils Brünner and Jan Stenvang are co-founders of Scandion Oncology, which owns the rights to SCO-101. No other authors declared any conflict of interest.