Tumor Subtype Determines Therapeutic Response to Chimeric Polypeptide Nanoparticle-based Chemotherapy in
Animals
CD8-Positive T-Lymphocytes
/ drug effects
Cell Line, Tumor
Disease Models, Animal
Doxorubicin
/ administration & dosage
Drug Carriers
/ chemistry
Drug Screening Assays, Antitumor
Humans
Mice
Mice, Knockout
Micelles
Nanoparticles
/ chemistry
Nerve Sheath Neoplasms
/ drug therapy
PTEN Phosphohydrolase
/ genetics
Peptides
/ chemistry
Sarcoma
/ drug therapy
Tissue Distribution
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
15 09 2020
15 09 2020
Historique:
received:
07
08
2019
revised:
07
04
2020
accepted:
20
07
2020
pubmed:
29
7
2020
medline:
15
12
2021
entrez:
29
7
2020
Statut:
ppublish
Résumé
Nanoparticle-encapsulated drug formulations can improve responses to conventional chemotherapy by increasing drug retention within the tumor and by promoting a more effective antitumor immune response than free drug. New drug delivery modalities are needed in sarcomas because they are often chemoresistant cancers, but the rarity of sarcomas and the complexity of diverse subtypes makes it challenging to investigate novel drug formulations. New drug formulations can be tested in animal models of sarcomas where the therapeutic response of different formulations can be compared using mice with identical tumor-initiating mutations. Here, using Cre/loxP and CRISPR/Cas9 techniques, we generated two distinct mouse models of The CP-Dox formulation was superior to free doxorubicin in MPNST models. However, in UPS tumors, CP-Dox did not improve survival in comparison with free doxorubicin. While CP-Dox treatment resulted in elevated intratumoral doxorubicin concentrations in MPNSTs, this increase was absent in UPS tumors. In addition, elevation of CD8 These results have important implications for treating sarcomas with nanoparticle-encapsulated chemotherapy by highlighting the tumor subtype-dependent nature of therapeutic response.
Identifiants
pubmed: 32718998
pii: 1078-0432.CCR-19-2597
doi: 10.1158/1078-0432.CCR-19-2597
pmc: PMC7641033
mid: NIHMS1615499
doi:
Substances chimiques
Drug Carriers
0
Micelles
0
Peptides
0
Doxorubicin
80168379AG
PTEN Phosphohydrolase
EC 3.1.3.67
Pten protein, mouse
EC 3.1.3.67
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5036-5047Subventions
Organisme : NIGMS NIH HHS
ID : T32 GM067795
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA086862
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA197616
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM145449
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007337
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007171
Pays : United States
Organisme : NCI NIH HHS
ID : F30 CA206424
Pays : United States
Informations de copyright
©2020 American Association for Cancer Research.
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