# Salinomycin and its binding protein nucleolin in neuroblastoma

> **NIH NIH R21** · BAYLOR RESEARCH INSTITUTE · 2022 · $185,247

## Abstract

Project Summary/Abstract
Neuroblastoma (NB) develops from immature nerve cells of the sympathetic nervous system, thus, they can be
found anywhere along the sympathetic nervous system, although the majority arise in the adrenal glands. NB is
one of the most commonly diagnosed solid tumors in infants, and a leading cause of mortality in children with
solid tumors, accounting for 15% of all malignancy-related death in early childhood. Major obstacles in the clinical
management of NB are therapy resistance, and undesirable post treatment side effects of current therapies.
Research advances during recent years indicate that treatment resistance in these patients is attributable to the
presence of cancer stem cells (CSCs) in NBs that are refractory to conventional anti-cancer drugs such as
carboplatin and cyclophosphamide. However, efforts to develop new effective molecular agents for NB
recurrence and therapy resistance remain unsatisfactory. One critical barrier to achieving successful
therapeutics is the heterogeneity of NB: a disorder we think of as a single disease entity exhibits in fact
biologically heterogeneous conditions that converge on common clinical phenotypes. From the perspectives of
genotype (e.g., MYCN amplification), risk stratification (e.g., low, intermediate, high), and clinical behavior (e.g.,
stage of disease and histology), NB is heterogeneous. Based on the above mentioned needs, we are to explore
new treatment strategies for NB. While many distinct pathways and CSC biomarkers have been implicated in
NB, we have developed a novel paradigm to develop an effective treatment for NB. First, we showed that
salinomycin exhibits strong cytotoxicity against NB cells and NB-CSCs. Further, we convincingly demonstrated
that nucleolin (NCL) is a salinomycin’s binding protein in NB cells. We then found that NCL is linked with CD34
in NB cells. Both NCL and CD34 are rarely explored in NB. These exciting findings prompt us to study therapeutic
activity of salinomycin and potential to stratify patients who are versus are not responsive to this therapy based
on its binding target NCL’s expression and to explore the mechanisms of drug action of salinomycin as a potential
NB therapeutic. Development of new clinically effective treatment strategies for patients with NB remains a
challenging task, and is a long-term goal of the proposed project. The immediate overall objective of the proposed
work is to investigate the therapeutic effect of salinomycin, potentially to stratify patients by their therapy
responses based on NCL expression and explore the underlying cytotoxic mechanism of salinomycin against
NB in vitro and in vivo. Our central hypothesis is that salinomycin functions through binding to an intracellular
target that initiates a signaling cascade involving the control of NB cell growth and tumor bulk formation. This
project will explore 1) how NCL mediates the anti-tumor effects of salinomycin in NB, and 2) the role of the NCL-
CD34 pro...

## Key facts

- **NIH application ID:** 10361595
- **Project number:** 1R21CA267885-01
- **Recipient organization:** BAYLOR RESEARCH INSTITUTE
- **Principal Investigator:** Erxi Wu
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $185,247
- **Award type:** 1
- **Project period:** 2022-02-07 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10361595

## Citation

> US National Institutes of Health, RePORTER application 10361595, Salinomycin and its binding protein nucleolin in neuroblastoma (1R21CA267885-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10361595. Licensed CC0.

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