ELife: a new strategy for targeting common cancers

March 30, 2019 / BIOON / - a new study published in eLife found that a protein is necessary for the survival of a specific cancer cell This study was first published on biorxiv and found that a protein called Werner syndrome helicase (WRN) is a new target for the treatment of tumor patients with high microsatellite instability high (MSI-H) Photo source: eLife MSI is a feature of cancer cells Its DNA mismatch repair (MMR) system is defective About 4% of cancer patients have MMR defects and MSI-H, especially in colorectal cancer, endometrial cancer and gastric cancer The approval of immunotherapeutics pembrolizumab, nivolumab and ipilimumab has changed the treatment status of MSI-H patients Although these drugs will cause long-term positive reactions, they will eventually produce drug resistance, so more effective treatment drugs are needed "Cancer targeting therapy is mainly aimed at the unique biological characteristics of tumor cells, rather than the characteristics of normal cells." Simon w ö hrle, a scientist at the Berlin Ingelheim Research Center (RCV) in Vienna, Austria, who is the study's co-author, said "Before we can develop new therapies for MSI-H cancer, we need to understand what factors contribute to the survival and proliferation of cancer cells." The team used MSI-H cancer cell lines and recent cell line screening to answer this question They found that eliminating the WRN function of MSI-H cells prevented the cells from working normally, resulting in cell division defects "In particular, we found chromosomal damage and genomic instability in MSI-H cancer cell lines with WRN removed, indicating that WRN is the weakness of MSI-H cells." Mark petronczki, co-author of the study and director of cancer cell signaling at RCV in Brigham, said WRN deficiency has been known to cause Warner's syndrome, a disease of early aging associated with an increased risk of cancer, so it is believed to play a key role in the suppression of cancer But contrary to conventional wisdom, the study found that WRN plays a survival promoting role in specific cancer cells "We have demonstrated the role of combining deep functional genomic data with tumor cell lineages in the search for tumor drug targets." Mark Pearson, another co-author of the study and vice chairman of RCV at bringer ingelham, said "Our research shows that drug inhibition of WRN function is a potential therapeutic target for MSI-H tumors, which can help us develop more effective drugs." Reference: Simone Lieb et al, Werner syndrome helicase is a selective vulnerability of microsatellite installation high tutorial cells, eLife (2019) Doi: 10.7554/elife.43333