A rectal cancer organoid platform to study individual responses to chemoradiation.
Journal
Nature medicine
ISSN: 1546-170X
Titre abrégé: Nat Med
Pays: United States
ID NLM: 9502015
Informations de publication
Date de publication:
10 2019
10 2019
Historique:
received:
03
12
2018
accepted:
15
08
2019
pubmed:
9
10
2019
medline:
22
1
2020
entrez:
9
10
2019
Statut:
ppublish
Résumé
Rectal cancer (RC) is a challenging disease to treat that requires chemotherapy, radiation and surgery to optimize outcomes for individual patients. No accurate model of RC exists to answer fundamental research questions relevant to patients. We established a biorepository of 65 patient-derived RC organoid cultures (tumoroids) from patients with primary, metastatic or recurrent disease. RC tumoroids retained molecular features of the tumors from which they were derived, and their ex vivo responses to clinically relevant chemotherapy and radiation treatment correlated with the clinical responses noted in individual patients' tumors. Upon engraftment into murine rectal mucosa, human RC tumoroids gave rise to invasive RC followed by metastasis to lung and liver. Importantly, engrafted tumors displayed the heterogenous sensitivity to chemotherapy observed clinically. Thus, the biology and drug sensitivity of RC clinical isolates can be efficiently interrogated using an organoid-based, ex vivo platform coupled with in vivo endoluminal propagation in animals.
Identifiants
pubmed: 31591597
doi: 10.1038/s41591-019-0584-2
pii: 10.1038/s41591-019-0584-2
pmc: PMC7385919
mid: NIHMS1575945
doi:
Substances chimiques
Fluorouracil
U3P01618RT
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
1607-1614Subventions
Organisme : NCI NIH HHS
ID : R01 CA193837
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA009207
Pays : United States
Organisme : NCI NIH HHS
ID : K22 CA181280
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA092629
Pays : United States
Organisme : NCI NIH HHS
ID : F30 CA200110
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA155169
Pays : United States
Organisme : NCI NIH HHS
ID : K08 CA230213
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA094060
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA224079
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007739
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA129243
Pays : United States
Organisme : NCI NIH HHS
ID : K12 CA184746
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA160001
Pays : United States
Organisme : NIH HHS
ID : U54 OD020355
Pays : United States
Organisme : NCI NIH HHS
ID : R25 CA020449
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA182551
Pays : United States
Commentaires et corrections
Type : CommentIn
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