# Project 1 - High Throughtput Drug Screening and Correlations with Mutational Status in Myeloma Cell Lines and Patient Samples

> **NIH NIH U54** · MAYO CLINIC ARIZONA · 2021 · $314,462

## Abstract

PROJECT 1 SUMMARY/ABSTRACT 
Despite recent advances in therapy the majority of multiple myeloma (MM) patients are not cured but rather 
suffer from a chronic relapsing, yet ultimately fatal disease. Two challenges immediately become evident. Most 
urgent is the need to find alternative therapies for patients who fail existing potent drug classes. Second, is to 
understand why patients may be resistant in the first place and to seek methodologies, dosing strategies and 
new drug combinations which can prevent or overcome drug-resistant relapse. 
We propose an innovative strategy of “direct to drug” screening of 500 primary patient samples with 
chemogenomic interrogation which addresses both of these two big questions. Our hypothesis is that a direct 
to drug analysis of individual patients will improve response rates, lower unnecessary toxicity and reduce drug 
costs through identification of the most effective combinations of FDA approved drugs for each patient. This 
strategy will also, for the purposes of this proposal, provide a database of samples and clinical data sets from 
which to explore genomic or clinical correlates of drug sensitivity and resistance. 
Our goal will be attained through the successful pursuit of three specific aims, building upon extensive cell line 
and primary patient sample data. First, we will measure the in vitro sensitivity of 79 MM therapeutics including 
CTEP compounds in 500 primary myeloma patient samples. Second, we will conduct combination screens to 
seek synergistic combinations of IMiDs and proteasome inhibitors as base compounds with other active MM 
therapeutics such as bromodomain inhibitors which can be tested in animal models such as the human CRBN 
mouse in project 2. Third, using our M3P mutation panels, we will conduct a chemogenomic interrogation to 
examine specific correlates of drug sensitivity and resistance utilizing pre-treatment and surviving cells from 
primary patient robotic screens. These studies will determine the frequency of specific genetic mutation or 
cellular subsets resistant to the most active drugs or drug combinations used in MM therapy and will be shared 
throughout the program for further epigenetic and transcriptional analysis and bi-directional feedback derived 
from both Projects 2 and 3. 
Critical to the current U54 application this strategy will provide a database of 500 multiple myeloma samples 
and linked clinical data sets which together build a mosaic of drug sensitivity and clinical phenotype from which 
all elements of this program grant can exploit to explore genomic or clinical correlates of drug sensitivity and 
resistance.

## Key facts

- **NIH application ID:** 10232129
- **Project number:** 5U54CA224018-04
- **Recipient organization:** MAYO CLINIC ARIZONA
- **Principal Investigator:** Peter Leif Bergsagel
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $314,462
- **Award type:** 5
- **Project period:** 2020-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10232129

## Citation

> US National Institutes of Health, RePORTER application 10232129, Project 1 - High Throughtput Drug Screening and Correlations with Mutational Status in Myeloma Cell Lines and Patient Samples (5U54CA224018-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10232129. Licensed CC0.

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