We propose, therefore, that efforts should be doubled to identify cancers potentially driven by aberrant alternative TrkAIII splicing in order to extend potential therapeutic options to include small molecule Trk tyrosine kinase inhibitors, inhibitors of PI3K/Akt/NF-кB signaling, inhibitors of Bcl-2 protein family and/or SOD2 expression, reversal of alternative TrkAIII splicing or novel TRAIL or TRAIL-receptor agonist formulations. Here, SOD2 is linked to cancer.