# Targeting the MYC Pathway for the Treatment of Cancer

> **NIH NIH R35** · STANFORD UNIVERSITY · 2023 · $945,225

## Abstract

Abstract
MYC is the most commonly activated oncogene in human cancer. However, to date, no existing therapies
directly target MYC or the MYC pathway. My goal is now to target the MYC oncogene pathway to treat human
cancer. Over the last 20 years, I have gained fundamental new insights into how the MYC oncogene initiates
and maintains tumorigenesis. My work has established the idea that MYC is a hallmark of cancer and that many
cancers are “MYC oncogene addicted”. I have identified both tumor intrinsic and host-immune dependent
mechanisms. Now, I will use these insights from lab and novel methods to develop new therapies for cancer. I
was one of the first investigators to use the Tetracycline regulatory system (Tet system) to generate “conditional”
transgenic mouse models to demonstrate that MYC-induced cancer is “reversible” or “oncogene addicted”
(Felsher and Bishop, Molecular Cell, 1999). Since then, I have used the Tet system to make a library of
oncogene driven transgenic mouse models (MYC, RAS, BCR-ABL) of T-cell acute lymphoma (T-ALL), leukemia
(AML), osteosarcoma (OS), hepatocellular carcinoma (HCC), lung adenocarcinoma (LAC) and renal cell
adenocarcinoma (RCC). I have used my conditional transgenic mouse model systems to not only understand
how MYC and other oncogenes initiate and maintain tumorigenesis but also develop innovative methods and
novel technologies to make seminal contributions in cancer research, exhibiting sustained productivity. My
proposed future research is built on recent observations that have used combined RNA, ChIP and metabolomic
analysis to identify that lipogenesis and CRISPR synthetic lethal screen to identify nuclear transport as examples
of otherwise not known to be MYC-regulated gene pathways that when targeted can block and reverse MYC-
driven cancer. Now, I propose to use my library of conditional transgenic mouse models and human PDX models
to generally identify targetable genes and pathways in the MYC oncogene pathway. I will use three
complimentary approaches: RNAseq, ChIPseq and DESI-MSI to identify novel vulnerabilities in MYC-driven
cancers; CRISPR in vitro and in vivo synthetic lethal screens combined with CyTOF and CODEX analysis to
identify targets in my MYC-driven tumor models and understand their mechanistic role in tumorigenesis; MYC
function reporter systems to be able to screen for genes and therapies to target MYC-driven cancers. My
proposed research program has extensive support from an interdisciplinary team of colleagues. My proposed
studies will glean novel mechanistic insights for how MYC drives tumorigenesis and use these insights to develop
new therapeutic targets.

## Key facts

- **NIH application ID:** 10693915
- **Project number:** 5R35CA253180-04
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** DEAN W FELSHER
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $945,225
- **Award type:** 5
- **Project period:** 2020-09-08 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10693915

## Citation

> US National Institutes of Health, RePORTER application 10693915, Targeting the MYC Pathway for the Treatment of Cancer (5R35CA253180-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10693915. Licensed CC0.

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