# Core 2: Stanford Breast Metastasis Center Organoid Core

> **NIH NIH U54** · STANFORD UNIVERSITY · 2021 · $263,348

## Abstract

Abstract/Project Summary
Breast cancer research is substantially hampered by lack of experimental models that efficiently reflect
physiological disease necessary to provide a comprehensive understanding of metastatic disease. Conventional
cell lines and PDX models have contributed greatly to our understanding of breast cancer biology, but are
inefficiently derived, do not fully capture the heterogeneity across breast cancer subtypes and rarely mimic
clinical observations. Advancements in 3D organoid models from our lab and others have shown that patient-
derived organoids (PDOs) can be generated efficiently, retain histologic and genetic features of originating tumor,
closely mimic patient drug response and are amendable to scale for genomic functional screens. Recently, the
Kuo lab developed next generation PDOs by developing an Air-Liquid Interface (ALI) culture system that enables
culture of tumor epithelium en bloc with endogenous immune stroma (Cell, 2018). The advent of ALI organoid
culture provides critical experimental models for studying the tumor microenvironment. Here, the Organoid Core
provides essential patient derived organoid models for identifying the evolutionary dynamics and
microenvironmental determinants of metastatic breast cancer for Stanford Breast Metastasis Center
investigators.
 Co-led by breast cancer genomics expert Dr. Christina Curtis and organoid pioneer Dr. Calvin Kuo,
the Stanford Breast Metastasis Center Organoid Core is uniquely positioned and qualified to address the
unmet needs highlighted in this RFA: Metastasis Research Network, by providing novel experimental models to
study metastatic dissemination patterns, cellular microenvironment crosstalk, and drug response. Here, the
organoid core will provide patient-derived breast cancer submerged organoids from primary and metastatic
tissue to study targeted drug resistance and to define specific metastatic patterns of breast cancer sub-clones
in Project 1, along with genomic functional screens using CRISPR/CAS9 and macrophage-mediated
phagocytosis in Project 3. Novel human breast cancer ALI organoid models will be extensively characterized
as compared to originating tissue in collaboration with Projects 1 and 2. Further, ALI culture conditions will be
optimized for functional tumor-immune crosstalk studies with Project 3. Upon successful completion, novel
organoid models will provide critical experimental tools for defining metastatic driver genes and identifying
therapeutic targets to overcome drug resistance and immune evasion.

## Key facts

- **NIH application ID:** 10272393
- **Project number:** 1U54CA261719-01
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** CALVIN J KUO
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $263,348
- **Award type:** 1
- **Project period:** 2021-09-14 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10272393

## Citation

> US National Institutes of Health, RePORTER application 10272393, Core 2: Stanford Breast Metastasis Center Organoid Core (1U54CA261719-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10272393. Licensed CC0.

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