# PROTECT (Harnessing PROTEin degradation for Advanced Childhood Tumors)

> **NIH NIH OT2** · DANA-FARBER CANCER INST · 2024 · $1,355,618

## Abstract

Abstract:
Background
Survival rates for children with solid tumors, including brain, have largely plateaued
over the past three decades making them the most common cause of disease-related
mortality in this age group. After decades of optimizing chemotherapy and
radiotherapy protocols, higher cure rates for childhood solid tumors will no longer be
achieved by “more of the same.” Rather, cures will require innovative interventions
that specifically target the unique biology of these tumors, which are often driven by
oncogenic fusions and other pediatric-specific oncoproteins historically considered
difficult drug targets. With advances in targeted protein degradation and chemical
interventions to inhibit protein-protein interactions, it has recently become tractable to
target these proteins previously thought to be “undruggable”. Moreover, unbiased
functional screening approaches, such as CRISPR-Cas9, have revealed new
pediatric cancer synthetic lethal liabilities in need of targeted inhibitors.
Aims
We aim to lead the transformation of delivering such specific treatments to our young
patients harnessing the power of a highly interdisciplinary and collaborative team of
world-leading experts in pediatric oncology, targeted protein degradation, high-
throughput chemical screening, medicinal chemistry, structural biology, tumor
biology, preclinical drug testing, and clinical trials, complemented by a trans-Atlantic
group of engaged patient representatives.
Methods
A bold plan will be pursued with a portfolio of projects that balance very high-risk
efforts with others nearing clinical implementation. We will focus on drivers/targets in
the following diseases: Ewing sarcoma, neuroblastoma, synovial sarcoma,
ependymoma and high-grade glioma. We will explore different approaches to target
these as yet undrugged paediatric drivers/dependencies, to overcome resistance to
available targeted inhibitors, and to improve the efficacy and therapeutic window of
CAR-T treatments.
How the results will be used
The aspiration of our team is to establish a sustainable platform for repeated
developmental cycles of paediatric-specific drug development for emerging targets
including a viable financial model to de-risk such developments for such rare
pediatric tumors to the direct benefit of our patients. Specifically, we anticipate
success through (i) delivering at least one optimised protein degrader for its
application in early-phase clinical trials, (ii) enabling the druggability of previously
“undruggable” targets, (iii) providing mechanistic insights into disease, novel targets,
and therapy resistance mechanisms and ways to tackle them.

## Key facts

- **NIH application ID:** 11047026
- **Project number:** 1OT2CA297572-01
- **Recipient organization:** DANA-FARBER CANCER INST
- **Principal Investigator:** Kimberly Stegmaier
- **Activity code:** OT2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,355,618
- **Award type:** 1
- **Project period:** 2024-05-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11047026

## Citation

> US National Institutes of Health, RePORTER application 11047026, PROTECT (Harnessing PROTEin degradation for Advanced Childhood Tumors) (1OT2CA297572-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/11047026. Licensed CC0.

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