# Project 3 - Modeling Proteasome Inhibitor Response and Resistance in Cell Lines and Patient Samples with Single Cell Analysis of Subpopulations

> **NIH NIH U54** · MAYO CLINIC ARIZONA · 2021 · $287,697

## Abstract

PROJECT 3 ABSTRACT 
MM is a plasma cell neoplasm within the bone marrow with significant complexity and heterogeneity at the 
molecular level. Despite improvements in the clinical outcomes achieved with newer therapies, wide inter- 
individual variation in response to treatment is a major limitation in achieving consistent therapeutic effects, or 
cures. Not all patients respond to initial therapies (innate resistance), and those that do frequently relapse with 
refractory disease (acquired resistance). The central hypothesis we are addressing is that rational therapeutic 
development in MM should be based on an understanding of the underlying genetics and biology of the tumor 
that identify sensitivity and resistance to current and future drugs. In this Myeloma-DRSC we are proposing 3 
Projects that will: 1) develop a high throughput drug screening platform for myeloma cell lines representing the 
wide diversity of MM biology; and use this platform to screen primary patient tumor cells for most effective 
responses, including combination therapies; 2) develop a comprehensive mutational and germline variation 
panel that will be correlated to drug responses in vitro and in vivo, as well as toxicities; 3) identify the 
mechanism of response and resistance for two of the most common therapeutics used in MM treatment: 
IMiDS and proteasome inhibitors; 4) develop genetic and immunophenotypic signatures that effectively predict 
tumor response, resistance, and patient toxicities; 5) identify tumor sub-populations that may contribute to 
emerging resistance; and 6) identify strategies to predict drug resistance and approaches to overcome 
resistance.

## Key facts

- **NIH application ID:** 10232132
- **Project number:** 5U54CA224018-04
- **Recipient organization:** MAYO CLINIC ARIZONA
- **Principal Investigator:** BRIAN G VAN NESS
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $287,697
- **Award type:** 5
- **Project period:** 2017-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10232132

## Citation

> US National Institutes of Health, RePORTER application 10232132, Project 3 - Modeling Proteasome Inhibitor Response and Resistance in Cell Lines and Patient Samples with Single Cell Analysis of Subpopulations (5U54CA224018-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10232132. Licensed CC0.

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