Combined MEK and YAP inhibition in a mouse model of neuroblastoma: A promising approach for minimal residual disease

jpedsurg.org

The cure rate of high-risk neuroblastoma remains unsatisfactory, necessitating the development of novel therapies. We previously reported the in vitro and in vivo efficacy of trametinib (TR), a MEK inhibitor, in neuroblastoma. The administration of TR further prolonged survival in a mouse model of neuroblastoma with minimal residual disease (MRD), which mimics post-tumorectomy residuals. However, the acquisition of resistance to long-term TR administration with YAP activation in the Hippo pathway remains an issue.

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Article · Oct 2025 · 1 min read

In brief

This study investigates combined MEK and YAP inhibition as a strategy to overcome resistance in high-risk neuroblastoma treatment. Using a mouse model mimicking post-surgical minimal residual disease, researchers address the challenge of YAP-mediated resistance that develops during long-term trametinib therapy.

Trametinib (MEK inhibitor) shows efficacy in neuroblastoma models and prolongs survival in minimal residual disease settings.
Long-term trametinib monotherapy leads to resistance via YAP activation in the Hippo pathway.
Combined MEK and YAP inhibition may overcome resistance mechanisms in high-risk neuroblastoma treatment.
Minimal residual disease mouse models effectively mimic post-surgical residual tumor for therapy testing.

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