# Project 5: Tumor Suppressor and Tumor Maintenance Genes

> **NIH NIH P01** · COLD SPRING HARBOR LABORATORY · 2021 · $630,426

## Abstract

Summary
The project has historically studied the action of tumor suppressor genes, and is based on the premise that
tumor suppressors reveal key regulatory nodes in growth control processes and the strategies nature uses to
combat cancer. Based on our observation that certain oncogenes promote apoptosis through p53, we initially
explored the mechanisms by which p53 suppressed apoptosis and how disruption of p53 network components
promoted tumorigenesis and impacted therapy response. Taking advantage of program collaborations, we
later established how p53 loss sustains tumorigenesis and, by combining oncogenomics, functional genomics,
and in vivo genetic screens, established the functional relevance of many cancer drivers. Over the last funding
cycle, we expanded our efforts towards understanding how tumor suppressor loss is required for tumor
maintenance, showing that re-establishing tumor suppressor networks can have profound and distinct anti-
proliferative effects, even in advanced cancers. This evolution spawned our current interest in “tumor
maintenance genes” – genes needed to sustain cancer progression – and stimulated the development of new
mouse models that enable suppression and/or reactivation of gene function at different stages of disease.
Moving forward, the project will focus on the identification and characterization of tumor suppressor and tumor
maintenance genes in hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) – two primary liver
cancers for which genomic studies have identified few “druggable” cancer drivers, and for which no effective
therapies exist. As such, we now propose to characterize how mutations in certain chromatin-modifying genes
– which are common in human tumors but are poorly understood - drive tumor initiation and maintenance, and
to implement new genetic and genomic tools to identify and validate therapeutic targets for primary liver
cancers driven by these altered gene products. Our approach combines mouse models, genetic tools, and
cancer genomics in a coordinated manner that enables the comprehensive interrogation of tumor suppressor
and tumor maintenance network, and benefits from multiple interactions with other projects and cores. The
project will produce a more complete understanding of how primary liver cancers are initiated and maintained
while simultaneously validating new therapeutic targets for these diseases. As such, our project addresses an
urgent and unmet clinical need.

## Key facts

- **NIH application ID:** 10092138
- **Project number:** 5P01CA013106-49
- **Recipient organization:** COLD SPRING HARBOR LABORATORY
- **Principal Investigator:** SCOTT W. LOWE
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $630,426
- **Award type:** 5
- **Project period:** 1997-02-10 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10092138

## Citation

> US National Institutes of Health, RePORTER application 10092138, Project 5: Tumor Suppressor and Tumor Maintenance Genes (5P01CA013106-49). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10092138. Licensed CC0.

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