Modeling biological and genetic diversity in upper tract urothelial carcinoma with patient derived xenografts.
Aged
Animals
Antibodies, Monoclonal, Humanized
/ pharmacology
Antineoplastic Agents
/ pharmacology
Biopsy
Camptothecin
/ analogs & derivatives
Carcinoma, Transitional Cell
/ genetics
Female
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Genetic Variation
High-Throughput Nucleotide Sequencing
Humans
Immunoconjugates
/ pharmacology
Interleukin Receptor Common gamma Subunit
/ genetics
Male
Mice
Mice, Inbred NOD
Mice, SCID
Middle Aged
Mutation
Neoplasm Metastasis
Neoplasm Transplantation
Phenotype
Precision Medicine
Prospective Studies
Quinolines
/ pharmacology
Retrospective Studies
Sequence Analysis, RNA
Trastuzumab
Urinary Bladder Neoplasms
/ genetics
Urothelium
/ pathology
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
24 04 2020
24 04 2020
Historique:
received:
11
09
2019
accepted:
24
03
2020
entrez:
26
4
2020
pubmed:
26
4
2020
medline:
4
8
2020
Statut:
epublish
Résumé
Treatment paradigms for patients with upper tract urothelial carcinoma (UTUC) are typically extrapolated from studies of bladder cancer despite their distinct clinical and molecular characteristics. The advancement of UTUC research is hampered by the lack of disease-specific models. Here, we report the establishment of patient derived xenograft (PDX) and cell line models that reflect the genomic and biological heterogeneity of the human disease. Models demonstrate high genomic concordance with the corresponding patient tumors, with invasive tumors more likely to successfully engraft. Treatment of PDX models with chemotherapy recapitulates responses observed in patients. Analysis of a HER2 S310F-mutant PDX suggests that an antibody drug conjugate targeting HER2 would have superior efficacy versus selective HER2 kinase inhibitors. In sum, the biological and phenotypic concordance between patient and PDXs suggest that these models could facilitate studies of intrinsic and acquired resistance and the development of personalized medicine strategies for UTUC patients.
Identifiants
pubmed: 32332851
doi: 10.1038/s41467-020-15885-7
pii: 10.1038/s41467-020-15885-7
pmc: PMC7181640
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Antineoplastic Agents
0
Il2rg protein, mouse
0
Immunoconjugates
0
Interleukin Receptor Common gamma Subunit
0
Quinolines
0
trastuzumab deruxtecan
5384HK7574
neratinib
JJH94R3PWB
Trastuzumab
P188ANX8CK
Camptothecin
XT3Z54Z28A
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
1975Subventions
Organisme : NIH HHS
ID : U54 OD020355
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA234361
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA221745
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA229624
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA082088
Pays : United States
Organisme : NCI NIH HHS
ID : K12 CA184746
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA221757
Pays : United States
Commentaires et corrections
Type : CommentIn
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