Detection of phenotype‐specific therapeutic vulnerabilities in breast cells using a CRISPR loss‐of‐function screen

Phenotypic heterogeneity hampers anticancer treatment efficacy. Here, we applied a CRISPR‐Cas9 loss‐of‐function screen of a ‘druggable genome’ in isogenic breast cell lines displaying opposing EMT phenotypes. We identified phenotype‐specific genetic vulnerabilities (alone or under ‘therapy pressure’) that represent actionable targets in distinct phenotypes: EGFR‐MAPK signaling in the epithelial phenotype, and G2‐M transition and FASN in the mesenchymal phenotype cells...