# Project 3. Oncogenomics to identify and validate novel targeted therapies in myeloma

> **NIH NIH P01** · DANA-FARBER CANCER INST · 2020 · $280,604

## Abstract

Project Summary (Project 3)
Our longstanding focus has been to understand the multiple myeloma (MM) cell- bone marrow stromal cell
(BMSC) interactions. We have utilized our in vitro and in vivo models of the MM cell in the bone marrow milieu
to identify molecular targets and pathways supporting myeloma cell growth, survival, and drug resistance, and
implement effective molecularly-based therapies with dramatic effects on the survival of MM patients.
Importantly, rather than focusing on individual targets, our studies integrating various genomic and epigenomic
parameters have identified gene regulatory networks as the fundamental mechanisms responsible for
continued MM cell growth, despite single targeted therapies. These recurrent and important network motifs
form functional nodes in the larger regulatory networks, and are considered to be linchpins of disease causing
genomic alterations in MM and other cancers. We hypothesize that aberrant molecular networks drive the
progression of MM; confer tumor cell growth and survival advantage; and affect clinical outcome; and that
disruption of such circuits will have therapeutic implications. In this project, our robust human MM model
systems will be used to stringently validate the role of novel regulatory circuits identified to be of
biologic/prognostic significance in Projects 1 and 2 or implicated in disease progression in Project 4; and
assess the therapeutic potential of targeting these circuits, both alone and in combination with established and
emerging MM therapeutics. We will use our advanced bioinformatic analytical methods to identify gene
regulatory networks dysregulated in myeloma and a pooled and/or gene-specific CRISPR screen to evaluate
functional impact of each component of the candidate regulatory networks (Specific Aim 1a,b); validate the
functional role of selected molecular targets regulating MM cell growth, survival, and drug resistance using our
in vitro and in vivo models of human MM in the bone marrow milieu (Specific Aim 1c,d); and evaluate the
impact of potential therapeutic agents directed against these validated novel molecular networks, alone and in
combination (Specific Aim 2). This proposal will thus improve our understanding of the regulatory circuitry that
controls tumor growth and progression in MM, and to develop the next generation of targeted therapies in MM.

## Key facts

- **NIH application ID:** 9987299
- **Project number:** 5P01CA155258-09
- **Recipient organization:** DANA-FARBER CANCER INST
- **Principal Investigator:** KENNETH C. ANDERSON
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $280,604
- **Award type:** 5
- **Project period:** 2011-12-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9987299

## Citation

> US National Institutes of Health, RePORTER application 9987299, Project 3. Oncogenomics to identify and validate novel targeted therapies in myeloma (5P01CA155258-09). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9987299. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*