A human breast cancer-derived xenograft and organoid platform for drug discovery and precision oncology.

Document Type

Article

Publication Date

2-1-2022

Publication Title

Nat Cancer

Keywords

JGM

JAX Source

Nat Cancer 2022 Feb; 3(2):232-250.

Volume

3

Issue

2

First Page

232

Last Page

250

ISSN

2662-1347

PMID

35221336

DOI

https://doi.org/10.1038/s43018-022-00337-6

Abstract

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.

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