Medium-throughput Drug Screening of Patient-derived Organoids from Colorectal Peritoneal Metastases to Direct Personalized Therapy.
Adult
Aged
Aged, 80 and over
Antineoplastic Agents
/ pharmacology
Australia
Colorectal Neoplasms
/ drug therapy
Drug Screening Assays, Antitumor
/ methods
Feasibility Studies
Female
High-Throughput Nucleotide Sequencing
Humans
Male
Middle Aged
Organoids
/ drug effects
Peritoneal Neoplasms
/ drug therapy
Peritoneum
/ cytology
Precision Medicine
/ methods
Primary Cell Culture
/ methods
Prospective Studies
Reproducibility of Results
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 07 2020
15 07 2020
Historique:
received:
07
01
2020
revised:
24
03
2020
accepted:
05
05
2020
pubmed:
8
5
2020
medline:
3
11
2021
entrez:
8
5
2020
Statut:
ppublish
Résumé
Patients with colorectal cancer with peritoneal metastases (CRPMs) have limited treatment options and the lowest colorectal cancer survival rates. We aimed to determine whether organoid testing could help guide precision treatment for patients with CRPMs, as the clinical utility of prospective, functional drug screening including nonstandard agents is unknown. CRPM organoids (peritonoids) isolated from patients underwent parallel next-generation sequencing and medium-throughput drug panel testing Peritonoids were successfully generated and validated from 68% (19/28) of patients undergoing standard care. Genomic and drug profiling was completed within 8 weeks and a formal report ranking drug sensitivities was provided to the medical oncology team upon failure of standard care treatment. This resulted in a treatment change for two patients, one of whom had a partial response despite previously progressing on multiple rounds of standard care chemotherapy. The barrier to implementing this technology in Australia is the need for drug access and funding for off-label indications. Our approach is feasible, reproducible, and can guide novel therapeutic choices in this poor prognosis cohort, where new treatment options are urgently needed. This platform is relevant to many solid organ malignancies.
Identifiants
pubmed: 32376656
pii: 1078-0432.CCR-20-0073
doi: 10.1158/1078-0432.CCR-20-0073
pmc: PMC8366292
mid: NIHMS1610765
doi:
Substances chimiques
Antineoplastic Agents
0
Types de publication
Journal Article
Multicenter Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3662-3670Subventions
Organisme : NCI NIH HHS
ID : R01 CA214428
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA217883
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA124488
Pays : United States
Informations de copyright
©2020 American Association for Cancer Research.
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