In this study, the authors performed an unbiased CRISPR–Cas9 knockout screen on melanoma cells that were both resistant and addicted to inhibition of the serine/threonine-protein kinase BRAF, in order to functionally mine their genome for ‘addiction genes’. Their results uncover a pathway that underpins drug addiction in cancer cells, which may help to guide the use of alternating therapeutic strategies for enhanced clinical responses in drug-resistant cancers.
In this study, the scientists used the CRISPR-Cas9 system to target exons encoding functional protein domains. A screen of 192 chromatin regulatory domains in murine acute myeloid leukemia cells identifies six known drug targets and 19 additional dependencies.
Discovering the function of a gene requires cloning a DNA sequence and expressing it. Until now, this was performed on a one-gene-at-a-time basis, causing a bottleneck. Scientists at Rutgers University-New Brunswick in collaboration with Johns Hopkins University and Harvard Medical School have invented a technology to clone thousands of genes simultaneously and create massive libraries of proteins from DNA samples, potentially ushering in a new era of functional genomics.
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In this study, the authors performed an unbiased CRISPR–Cas9 knockout screen on melanoma cells that were both resistant and addicted to inhibition of the serine/threonine-protein kinase BRAF, in order to functionally mine their genome for ‘addiction genes’. Their results uncover a pathway that underpins drug addiction in cancer cells, which may help to guide the use of alternating therapeutic strategies for enhanced clinical responses in drug-resistant cancers.