Multiple approaches to repurposing drugs for neuroblastoma

Area of Science:

• Oncology
• Pharmacology
• Computational Biology

Background:

• Neuroblastoma (NB) is a significant pediatric cancer with limited treatment options and low survival rates for high-risk patients.
• Drug repurposing offers a viable strategy for rare diseases like NB, leveraging existing approved or clinical-stage compounds.

Purpose of the Study:

• To identify potential drug candidates for neuroblastoma (NB) treatment through a drug repurposing approach.
• To evaluate the cytotoxicity of identified compounds against NB cell lines using in vitro assays and machine learning.

Main Methods:

• Utilized Bayesian machine learning, in vitro cell assays, and combination analysis to screen compounds.
• Assessed the cytotoxicity of pyronaridine, BAY 11-7082, niclosamide, and fingolimod against SH-SY5Y and SK-N-AS NB cell lines.
• Investigated drug combinations involving pyronaridine, etoposide, and crizotinib.

Main Results:

• Pyronaridine, BAY 11-7082, niclosamide, and fingolimod demonstrated significant cytotoxicity against NB cell lines.
• Pyronaridine showed antagonistic effects when combined with etoposide or crizotinib, while etoposide and crizotinib exhibited synergy.
• Structure-activity relationships of pyronaridine analogs were explored.

Conclusions:

• Identified multiple compounds with cytotoxic potential against neuroblastoma, suitable for drug repurposing.
• Further in vivo and in vitro studies are warranted to evaluate the translational potential of these compounds and their combinations for NB treatment.