# Research Project 2: Neuroblastoma

> **NIH NIH U54** · DANA-FARBER CANCER INST · 2024 · $268,579

## Abstract

Project Summary
 Radiopharmaceuticals have shown tremendous clinical promise, resulting in regulatory approvals of
several agents. Such targeted radiotherapy exposes tumor cells to continuous, exponentially decaying
radiation, resulting in biological effects distinct from those of external beam radiotherapy. Despite this
fundamental difference, there is limited understanding of the impact of radiopharmaceuticals on tumor cell
populations and other components of the tumor microenvironment such as stromal cells, immune
compartments, and endothelial cells. The proposed work will provide novel insights into tumor cell-intrinsic and
-extrinsic mechanisms of radiation response that can inform the study of radiopharmaceuticals across
oncology.
 Against this backdrop, Project 2 will deeply characterize samples, imaging, and data from a cohort of
children with high-risk neuroblastoma treated with the targeted radiopharmaceutical 131I-MIBG. In Aim 1, we
will evaluate pre-treatment tumor cell-intrinsic and tumor cell-extrinsic factors, including somatic and host
genomic variants, single cell and bulk transcriptomics, and DNA damage repair profiling. In Aim 2, we will
assess dynamic changes in these factors in response to 131I-MIBG therapy, including evaluation of tumor
materials resected after 131I-MIBG as well as serial circulating tumor DNA samples. In Aim 3, we will leverage
two large national studies to assess the late effects of 131I-MIBG in this vulnerable pediatric population. By the
conclusion of Project 2, we will understand predictors of response and toxicity following 131I-MIBG therapy and,
more fundamentally, will understand the changes in a comprehensive set of molecular markers reflective of
radiation biology following treatment with this radiopharmaceutical.
 We have embedded our work within the only randomized phase 3 trial of 131I-MIBG ever conducted,
COG ANBL1531 (NCT03126916). However, beyond our utilization of goal-oriented clinical trials to enable a
question-oriented, hypothesis-driven study plan in close collaboration with our Data Science and AI Cores,
Project 2 advances several transformative innovations. A major barrier limiting our understanding of the
biological effects of radiopharmaceuticals is a lack of paired tumor samples obtained before and after exposure
to radiation. Our work overcomes this barrier by exploiting our unique access to detailed, cross-sectional data
on long-term medical, psychological, and educational outcomes, coupled with paired, longitudinal biologic
specimens, dosimetry, serial images, data science, mechanistic computational modeling, and radiomics to
identify the critical changes in our markers of tumor heterogeneity that are associated with 131I-MIBG response
and late effects. Importantly, biospecimens are available from patients treated with or without 131I-MIBG
therapy on this trial, enabling us to validate specific markers as truly predictive rather than simply prognostic.
Finally, our proposal leve...

## Key facts

- **NIH application ID:** 10931440
- **Project number:** 5U54CA274516-02
- **Recipient organization:** DANA-FARBER CANCER INST
- **Principal Investigator:** Dipanjan Chowdhury
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $268,579
- **Award type:** 5
- **Project period:** 2023-09-19 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10931440

## Citation

> US National Institutes of Health, RePORTER application 10931440, Research Project 2: Neuroblastoma (5U54CA274516-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10931440. Licensed CC0.

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