Signaling-induced systematic repression of miRNAs uncovers cancer vulnerabilities and targeted therapy sensitivity

• DOI: 10.1016/j.xcrm.2023.101200
• Publication Date: 2023-09-20T15:03:34Z
• Authors: Alexander A. Wurm; Silke Brilloff; Sofia Kolovich; Silvia Schäfer; Elahe Rahimian; Vida Kufrin; Marius Bill; Zunamys I. Carrero; Stephan Drukewitz; Alexander Krüger; Melanie Hüther; Sebastian Uhrig; Sandra Oster; Dana Westphal; Friedegund Meier; Katrin Pfütze; Daniel Hübschmann; Peter Horak; Simon Kreutzfeldt; Daniela Richter; Evelin Schröck; Gustavo Baretton; Christoph Heining; Lino Möhrmann; Stefan Fröhling; Claudia R. Ball; Hanno Glimm
• Keywords: Druggability

Targeted therapies are effective in treating cancer, but success depends on identifying cancer vulnerabilities. In our study, we utilize small RNA sequencing to examine the impact of pathway activation microRNA (miRNA) expression patterns. Interestingly, discover that miRNAs capable inhibiting key members activated pathways frequently diminished. Building this observation, develop an approach integrates a low-miRNA-expression signature identify druggable target genes cancer. We train and validate colorectal cells extend it diverse models using patient-derived vitro vivo systems. Finally, demonstrate its additional value support genomic transcriptomic-based drug prediction strategies pan-cancer patient cohort from National Center for Tumor Diseases (NCT)/German Cancer Consortium (DKTK) Molecularly Aided Stratification Eradication (MASTER) precision oncology trial. conclusion, strategy can predict vulnerabilities with high sensitivity accuracy might be suitable future therapy recommendations variety subtypes.