College of

Veterinary Medicine

Researchers with the Oklahoma State University College of Veterinary Medicine are gaining new insight into how radiotherapy may influence the biology of progressive neuroblastoma, a high-risk childhood cancer.

A research team led by Dr. Natarajan Aravindan in the Department of Physiological Sciences recently published a study titled, “Radiotherapy Reconstitutes the Collapsed miRNome of Progressive Neuroblastoma and Promotes a Favorable Tumor Evolutionary Shift.” The study was published in Frontiers in Bioscience (Landmark Edition).

The research examines the role of microRNAs, or miRNAs, which help regulate gene activity and can influence processes such as tumor growth, differentiation, immune response and treatment resistance.

The team analyzed tumor samples from patients with high-risk, stage 4 neuroblastoma across three disease states: tumors collected at diagnosis, tumors from patients with progressive disease following intensive multimodal therapy, and residual tumors following treatment that included radiotherapy. The researchers found that progressive disease was associated with the loss of 167 miRNAs and molecular changes linked to aggressive tumor evolution, including stemness, immune evasion, cellular plasticity and therapy resistance.

Importantly, the addition of radiotherapy was associated with broad changes in the miRNA landscape. Researchers found that radiotherapy reversed 146 of the miRNAs lost during disease progression and induced an additional 179 miRNAs. These changes were associated with pathways involved in apoptosis, DNA-damage response, differentiation, immune signaling and the transition toward a less aggressive cellular state.

The researchers also observed changes in tumor tissue following radiotherapy, including increased differentiation and neuronal maturation, reduced tumor cell proliferation and increased p53 activity. Tumors following radiotherapy showed characteristics associated with a more differentiated, ganglioneuroma-like state compared with the poorly differentiated tumors observed in progressive disease.

These findings provide proof-of-concept evidence that radiotherapy may influence tumor biology beyond its established role in local tumor control. The work provides a foundation for further investigation into how miRNA signatures could potentially be used to understand disease progression, monitor response to radiotherapy and inform future treatment strategies.

The study represents a collaboration involving researchers from OSU’s Department of Physiological Sciences, OU Health Stephenson Cancer Center and the University of Oklahoma Health Sciences Center.