A human breast cancer-derived xenograft and organoid platform for drug discovery and precision oncology.
Journal
Nature cancer
ISSN: 2662-1347
Titre abrégé: Nat Cancer
Pays: England
ID NLM: 101761119
Informations de publication
Date de publication:
02 2022
02 2022
Historique:
received:
12
03
2021
accepted:
12
01
2022
entrez:
28
2
2022
pubmed:
1
3
2022
medline:
7
4
2022
Statut:
ppublish
Résumé
Models that recapitulate the complexity of human tumors are urgently needed to develop more effective cancer therapies. We report a bank of human patient-derived xenografts (PDXs) and matched organoid cultures from tumors that represent the greatest unmet need: endocrine-resistant, treatment-refractory and metastatic breast cancers. We leverage matched PDXs and PDX-derived organoids (PDxO) for drug screening that is feasible and cost-effective with in vivo validation. Moreover, we demonstrate the feasibility of using these models for precision oncology in real time with clinical care in a case of triple-negative breast cancer (TNBC) with early metastatic recurrence. Our results uncovered a Food and Drug Administration (FDA)-approved drug with high efficacy against the models. Treatment with this therapy resulted in a complete response for the individual and a progression-free survival (PFS) period more than three times longer than their previous therapies. This work provides valuable methods and resources for functional precision medicine and drug development for human breast cancer.
Identifiants
pubmed: 35221336
doi: 10.1038/s43018-022-00337-6
pii: 10.1038/s43018-022-00337-6
pmc: PMC8882468
mid: NIHMS1771511
doi:
Types de publication
Case Reports
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
232-250Subventions
Organisme : NCI NIH HHS
ID : U54 CA224076
Pays : United States
Organisme : NHGRI NIH HHS
ID : T32 HG008962
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA125123
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA224067
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA042014
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA217617
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA221303
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2022. The Author(s).
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