# Understanding Infantile Rhabdomyosarcoma Biology and Therapeutic Targets

> **NIH NIH R01** · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · 2024 · $28,465

## Abstract

PROJECT SUMMARY/ABSTRACT
Infantile rhabdomyosarcoma (RMS) is a newly identified and poorly understood aggressive cancer with immature
skeletal muscle properties that affects young children. Recent clinical sequencing efforts have identified a
spectrum of likely biologically related gene fusions that genetically define infantile RMS: the most common being
a fusion between two transcriptional co-activators with roles in normal muscle development, termed VGLL2-
NCOA2. Although we know the defining oncogenic event, there are no therapies targeting the genetics of the
disease. Thus, patients are treated with general chemotherapy, surgery, and radiation, often ineffectively or with
harsh long-term side effects. There is a pressing need to understand the biology of infantile RMS, contextualize
infantile RMS biology with other RMS sub-types, and leverage this information to delineate therapeutic targets.
Progress is limited by a lack of animal models, cell lines, and PDXs to study the disease dynamics. My long-term
goal is to integrate vertebrate zebrafish, mouse, cell culture models and patient samples to identify conserved
genetic programs for RMS tumorigenesis and novel therapeutic strategies. Toward that end, this project’s main
objective is to elucidate the underlying biology and therapeutic targets in fusion-oncogene driven infantile RMS.
Our central hypothesis is that VGLL2-NCOA2 leverages normal developmental programs, including ARF6, to
mediate infantile RMS tumorigenesis, and that targeting these pathways is a therapeutic opportunity. Our specific
aims will address this hypothesis by: (Aim 1) Delineating VGLL2-NCOA2 structure-function requirements for
tumorigenesis, (Aim 2) Establishing mechanisms of VGLL2-NCOA2 and ARF6 cooperation in
rhabdomyosarcoma, and (Aim 3) Determining VGLL2-NCOA2 muscle lineage context and temporal
prerequisites for tumorigenesis. Completing these studies at the interface of developmental and cancer biology
will generate significant new knowledge regarding fusion-oncogene leveraging of developmental programs and
will identify potential therapeutic targets. The proposed research is conceptually innovative because it leverages
a cross-species comparative oncology approach to pinpoint the most important molecular drivers in a new
disease, and it is experimentally innovative because it utilizes multiple new vertebrate (zebrafish and mouse)
infantile RMS models developed by our group. Successful execution of this project will generate exciting data
focused on delineating the basic biology of infantile rhabdomyosarcoma to directly impact and guide clinical care.

## Key facts

- **NIH application ID:** 10993483
- **Project number:** 3R01CA272872-02S1
- **Recipient organization:** RESEARCH INST NATIONWIDE CHILDREN'S HOSP
- **Principal Investigator:** Genevieve Claire Kendall
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $28,465
- **Award type:** 3
- **Project period:** 2022-09-22 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10993483

## Citation

> US National Institutes of Health, RePORTER application 10993483, Understanding Infantile Rhabdomyosarcoma Biology and Therapeutic Targets (3R01CA272872-02S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10993483. Licensed CC0.

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