Target expression is a relevant factor in synthetic lethal screens
Iman J. Schultz, Herjan J.T. Coelingh Bennink · Communications Biology · 2022
Synthetic lethal screens support the discovery of novel cancer drug targets 1 . In a recent issue of Communications Biology , Gilad et al. 2 performed a synthetic lethal CRISPR Cas9 dropout screen in the human, estrogen receptor positive breast cancer (BC) cell line MCF-7. They aimed to identify targets that increased the sensitivity of the MCF-7 cells to the small molecule inhibitor SI-12, which targets SRC-3, an essential transcriptional cofactor of the estrogen receptor. A key finding of their screen indicated that targeting certain olfactory receptors (ORs) might confer anti-tumor effects in BC. However, these ORs, and a number of other hits, are not expressed in MCF-7 cells, calling into question the setup of the screen and warranting the inclusion of transcriptome data into the analysis pipeline of genetic screens.