Fig. 6 |. Nonsense-mediated RNA decay modulatory therapy.

Shown is a step-by-step approach which may be used in the future to determine whether a given tumour is a candidate for nonsense-mediated RNA decay (NMD)-stimulatory therapy or NMD-inhibitory therapy. Genomic and transcriptomic sequencing analysis will provide genome-wide information on mutations and transcript Levels, which will define both normal and mutant mRNAs downregulated by NMD in a given tumour. With use of an algorithm, the data from a given tumour will allow the tumour to be defined as either having an ‘NMD pro-tumour’ phenotype or an ‘NMD antitumour’ phenotype, on the basis of what is known — in the future — about the role of NMD target mRNAs in the particular type of tumour being analysed (as determined by standard pathology analysis). Another factor that will be considered is the overall NMD magnitude in the tumour, which will be determined from transcriptome analysis. Low NMD magnitude (inferred by upregulated NMD target mRNAs) would suggest treatment with NMD-stimulatory therapy. High NMD magnitude (inferred by downregulated NMD target mRNAs) would suggest treatment with NMD-inhibitory therapy.