# Overcoming Drug Resistance in Multiple Myeloma

> **NIH NIH U54** · MAYO CLINIC ARIZONA · 2021 · $982,082

## Abstract

OVERALL 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:** 10232127
- **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:** $982,082
- **Award type:** 5
- **Project period:** 2017-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10232127

## Citation

> US National Institutes of Health, RePORTER application 10232127, Overcoming Drug Resistance in Multiple Myeloma (5U54CA224018-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10232127. Licensed CC0.

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