# Research Project 2: Identify and validate efficacious therapies for metastatic breast cancer

> **NIH NIH U54** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2024 · $301,767

## Abstract

PROJECT SUMMARY – PROJECT 2
We hypothesize that patient-derived models can be used to identify more effective treatments for metastatic breast
cancer that can be predicted using molecular biomarkers, and that these models can be used to accurately predict
and interrogate treatment resistance. We will use our large collection of PDX, organoid, and tissue slice culture
models established from patients at different stages of treatment (including longitudinal samples and
primary:metastatic pairs from the same patient) to investigate new therapies. We will capitalize on our new, very
extensive dataset of NCI-IND drug responses in tumor organoids isolated from PDX (PDxOs): We have screened
nearly 100 PDxO models comprising all breast cancer subtypes, each with 40-50 drugs. Effective “lead” therapies
have been validated in vivo in PDX models; there is high concordance between organoid and PDX data. Omics
data are available on all of the models, and are being used to identify biomarkers associated with responders or
non-responders, for each lead therapy. We will apply new computational algorithms to this rich dataset to
prioritize drugs that can be used in combination with standard therapy, or in combination with each other. The
primary outcome of this study will be new NCI-IND treatment regimens for metastatic breast cancer, using
patient-derived models as a preclinical tool to (1) evaluate the efficacy of many drugs and drug combinations
across a large number of different patients’ tumor models, and (2) identify the biomarkers of responding and non-
responding breast cancers for new therapies, in order to better inform clinical trial design.

## Key facts

- **NIH application ID:** 10909335
- **Project number:** 5U54CA224076-06
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Alana L. Welm
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $301,767
- **Award type:** 5
- **Project period:** 2017-09-25 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10909335

## Citation

> US National Institutes of Health, RePORTER application 10909335, Research Project 2: Identify and validate efficacious therapies for metastatic breast cancer (5U54CA224076-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10909335. Licensed CC0.

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