# Manipulating Aberrant Calcium Signaling to Target Relapsed High-Risk Neuroblastoma

> **NIH NIH R15** · WESTERN NEW ENGLAND UNIVERSITY · 2024 · $423,743

## Abstract

Project Summary (30 lines)
High-risk Neuroblastoma (HRNB) is an extracranial pediatric cancer in which up to 65% of patients are
resistant to therapies. Recent biomedical advances have improved treatment options for cancer patients. Yet,
there are no effective treatment for relapsed HRNB patients who have undergone treatment and experienced
tumor recurrence. Our long-term goal is to develop more effective treatments that target relapsed HRNB.
A key feature of HRNB that drives disease progression is aberrant calcium (Ca2+) signaling. This offers
targeted therapeutic potential for Ca2+ channel inhibitors. Other groups have made progress in creating and
identifying Ca2+ channel inhibitors that may be used for cancer treatment. Our group is taking an alternative
approach by targeting Ca2+ signals that promote NB progression that are unique to relapsed HRNB. The
proposed project will leverage the elevated levels of cytosolic Ca2+ in relapsed HRNB driven by enhanced
store-operated Ca2+ entry (SOCE) to promote mitochondrial Ca2+ overload and apoptosis. The hypothesis is
that the activation of autophagy prevents mitochondrial Ca2+ overload and apoptosis in relapsed HRNB that
otherwise might be prone to apoptosis due to the elevated SOCE. Therefore, combination treatment composed
of a novel drug 249 and an autophagy inhibitor will effectively kill relapsed HRNB.
Targeting the mitochondrial Ca2+ transporters to regulate apoptosis may offer a new therapeutic approach for
treating relapsed HRNB and a variety of cancers. A detailed understanding of mtCa2+ signaling will allow
targeting of the diseased tissue without deleterious effects on healthy tissue.
In addition, this work includes undergraduate and graduate student researchers, including those from
underrepresented minority groups. Therefore, this work will train the next generation of researchers and
increase diversity in the biomedical workforce.

## Key facts

- **NIH application ID:** 10795286
- **Project number:** 1R15CA277188-01A1
- **Recipient organization:** WESTERN NEW ENGLAND UNIVERSITY
- **Principal Investigator:** Dana-Lynn T Koomoa
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $423,743
- **Award type:** 1
- **Project period:** 2024-03-01 → 2027-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10795286

## Citation

> US National Institutes of Health, RePORTER application 10795286, Manipulating Aberrant Calcium Signaling to Target Relapsed High-Risk Neuroblastoma (1R15CA277188-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10795286. Licensed CC0.

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