Repository logo

Clinical prospects of WRN inhibition as a treatment for MSI tumours.

Published version

Change log


Morales-Juarez, David A  ORCID logo


The discovery of synthetic lethal interactions with genetic deficiencies in cancers has highlighted several candidate targets for drug development, with variable clinical success. Recent work has unveiled a promising synthetic lethal interaction between inactivation/inhibition of the WRN DNA helicase and tumours with microsatellite instability, a phenotype that arises from DNA mismatch repair deficiency. While these and further studies have highlighted the therapeutic potential of WRN inhibitors, compounds with properties suitable for clinical exploitation remain to be described. Furthermore, the complexities of MSI development and its relationship to cancer evolution pose challenges for clinical prospects. Here, we discuss possible paths of MSI tumour development, the viability of WRN inhibition as a strategy in different scenarios, and the necessary conditions to create a roadmap towards successful implementation of WRN inhibitors in the clinic.


Funder: ERC Synergy grant DDREAMM (855741)

Funder: CONACyT Cambridge Scholarship and additional support from a gift from La Fondation ARC (to SPJ)


Perspective, /631/67/1059/602, /631/67/1059/153, /631/67/1059, /631/154/53, /631/67/1059/2326, perspective

Journal Title

NPJ Precis Oncol

Conference Name

Journal ISSN


Volume Title


Springer Science and Business Media LLC
Wellcome Trust (206388/Z/17/Z)
European Commission Horizon 2020 (H2020) ERC (855741)