CRISPR Study of Cancer Gene Fusion Regions Finds Potential New Drug Targets
In potentially the first large-scale systematic analysis of thousands of cancer gene fusions, UK scientists have announced that one such fusion could be a novel drug target for a number of cancers. CRISPR editing was used to determine the most important gene fusions for cancer cell survival, before anticancer compounds were tested on them to see which might be repurposed to specifically target the fusions.
The newly uncovered gene fusion, YAP1-MAML2, was announced in Nature Communications journal. It was one of 8,000 fusions in cancer cell lines tested by the scientists, generating large-scale genomic and pharmacologic datasets for more than 1,000 cell lines across 43 types of cancer. Because fusion proteins also impact on clinical responses to therapy, the cell lines were tested against over 350 anticancer drugs.
The researchers found that around 90% of the analysed fusions are not important for cancer cell survival, though some may have functional relevance and offer new repurposing or drug development opportunities.
YAP1-MAML2 was previously reported in both nasopharyngeal carcinomas and in a patient with skin cancer, but was identified in this study as also a recurrent fusion in glioblastoma, ovarian cancer, and head and neck cancer cell lines.
The study also found new information on fusions involving RAF1, ROS1, and BRD4, potentially allowing for further repurposing of drugs against rare pancreatic, breast, and lung cancers.