OncoLoop: A Network-Based Precision Cancer Medicine Framework.
Journal
Cancer discovery
ISSN: 2159-8290
Titre abrégé: Cancer Discov
Pays: United States
ID NLM: 101561693
Informations de publication
Date de publication:
06 02 2023
06 02 2023
Historique:
received:
31
03
2022
revised:
22
08
2022
accepted:
10
11
2022
pubmed:
15
11
2022
medline:
8
2
2023
entrez:
14
11
2022
Statut:
ppublish
Résumé
Prioritizing treatments for individual patients with cancer remains challenging, and performing coclinical studies using patient-derived models in real time is often unfeasible. To circumvent these challenges, we introduce OncoLoop, a precision medicine framework that predicts drug sensitivity in human tumors and their preexisting high-fidelity (cognate) model(s) by leveraging drug perturbation profiles. As a proof of concept, we applied OncoLoop to prostate cancer using genetically engineered mouse models (GEMM) that recapitulate a broad spectrum of disease states, including castration-resistant, metastatic, and neuroendocrine prostate cancer. Interrogation of human prostate cancer cohorts by Master Regulator (MR) conservation analysis revealed that most patients with advanced prostate cancer were represented by at least one cognate GEMM-derived tumor (GEMM-DT). Drugs predicted to invert MR activity in patients and their cognate GEMM-DTs were successfully validated in allograft, syngeneic, and patient-derived xenograft (PDX) models of tumors and metastasis. Furthermore, OncoLoop-predicted drugs enhanced the efficacy of clinically relevant drugs, namely, the PD-1 inhibitor nivolumab and the AR inhibitor enzalutamide. OncoLoop is a transcriptomic-based experimental and computational framework that can support rapid-turnaround coclinical studies to identify and validate drugs for individual patients, which can then be readily adapted to clinical practice. This framework should be applicable in many cancer contexts for which appropriate models and drug perturbation data are available. This article is highlighted in the In This Issue feature, p. 247.
Identifiants
pubmed: 36374194
pii: 716310
doi: 10.1158/2159-8290.CD-22-0342
pmc: PMC9905319
mid: NIHMS1851760
doi:
Substances chimiques
Androgen Receptor Antagonists
0
Nitriles
0
Receptors, Androgen
0
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
386-409Subventions
Organisme : NCI NIH HHS
ID : R01 CA238005
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA261822
Pays : United States
Organisme : NIH HHS
ID : S10 OD012351
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA265768
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA013696
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA217858
Pays : United States
Organisme : NIH HHS
ID : S10 OD021764
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001873
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA163227
Pays : United States
Organisme : NCI NIH HHS
ID : R00 CA194287
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA272610
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA209997
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA097186
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA173481
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA221757
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA183929
Pays : United States
Informations de copyright
©2022 American Association for Cancer Research.
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