# Longitudinal models of breast cancer for studying mechanisms of therapy response and resistance

> **NIH NIH U01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2022 · $806,283

## Abstract

PROJECT ABSTRACT
The goal of this proposal is to test the fidelity of three types of patient-derived breast cancer models with regard
to genomic and epigenetic aberrations, clonal heterogeneity and evolution, and treatment response/resistance.
We will compare PDXs, patient-derived organoids (PDOs), and patient-derived conditionally-reprogrammed cells
(PDCRCs) from a total of 22 patients with breast cancer. The models will be derived from patient samples
acquired at 2-3 longitudinal time points during the patients’ cancer treatments. To our knowledge, this will be the
first effort to establish a triad of patient-derived models of cancer (PDMCs) in longitudinal series from breast
cancer patients undergoing standard clinical care. Importantly, the models will be associated with annotated
clinical data on patient treatment and outcomes. PDMCs will be functionally evaluated for their response to
patient-matched therapies. Aim 1 is focused on testing whether PDMCs from patients undergoing therapy
replicate clinicopathological, molecular, genomic and cellular phenotypes observed in the patients’ clinical
samples. PDMCs will be generated from viable breast cancer specimens obtained prior to and following patient
therapy – either in the neoadjuvant or metastatic setting. We will generate a triad of patient-matched PDMCs
(PDX, PDO, PDCRC) and compare tumor pathology, gene expression, WGS/WES, DNA methylation, CNV,
mutation profiles, and cellular clonality/heterogeneity between the patient tissue and PDMCs. Aim 2 will
investigate whether PDMCs appropriately model patient response to therapy – an assessment that is needed to
determine their potential application in basic research, drug discovery, and as predictors of optimal therapies for
patients undergoing treatment. PDMCs will be evaluated in a co-clinical study to test the concordance of response
between PDMCs and the clinical response observed in patients. We will also evaluate the concordance of PDOs
and PDMCs against a panel of FDA-approved cancer therapies, genomic-guided therapies, and investigate
whether the chemo-sensitivity of clones in PDOs and PDCRCs is associated with their observed clonal frequency
in patient tumors following treatment. Our study will not only determine whether PDMCs can model the repertoire
of breast cancer phenotypes, but will also determine, through a co-clinical study, whether they can functionally
replicate patient response to therapies.

## Key facts

- **NIH application ID:** 10457293
- **Project number:** 5U01CA217617-05
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Gabor T Marth
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $806,283
- **Award type:** 5
- **Project period:** 2018-09-06 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10457293

## Citation

> US National Institutes of Health, RePORTER application 10457293, Longitudinal models of breast cancer for studying mechanisms of therapy response and resistance (5U01CA217617-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10457293. Licensed CC0.

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