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. 2022 Nov 15;6:85. doi: 10.1038/s41698-022-00319-y

Fig. 1. Temporal differences in MSI and cancer development might lead to contrasting clinical outcomes upon WRN inhibition.

Fig. 1

Schematic outlining the possible paths towards developing MSI tumours with (TA)n repeat expansions that can be targeted with WRN inhibitors. Acquiring MMR deficiency, through germline and/or somatic alterations in MMR genes, is a necessary first step towards MSI and tumour development. MMR deficient cells can become cancerous before developing MSI and (TA)n repeat expansions (top branch) or develop MSI and (TA)n repeat expansions before becoming cancerous (bottom branch) potentially leading to different clinical outcomes. The therapeutic window of WRN inhibitors ultimately depends on MSI status and the degree of (TA)n repeat expansions. Microsatellite stable (MSS) and MSI cells with (TA)n repeat expansions are highlighted in yellow and red respectively. Figure was created with BioRender.com.