‘High-throughput RNAi screening reveals cancer-selective lethal targets in the RNA spliceosome’ in Oncogene.
Novel targets for selective treatment of lung cancer revealed.
Lung cancer is the most common and deadliest form of cancer. New treatment strategies are urgently awaited. To this end, Maxime Blijlevens (from the van Beusechem group) searches for specific vulnerabilities in lung cancer cells. Her focus is on the spliceosome, a huge complex of 364 proteins regulating RNA splicing. In a recent paper in Oncogene, the team describes the comprehensive interrogation of all spliceosome components for selective lethality in lung cancer cells versus non-malignant lung cells, using high-throughput RNA interference screening. They present the identification of a small 7-protein structure in the core of the spliceosome as particularly useful target for selective treatment of lung cancer. Silencing any of the 7 proteins induced apoptosis in lung cancer cells, but not in non-malignant cells. This was associated with a change in the RNA splicing pattern of an indicator gene in lung cancer cells to a variant that is typical for non-malignant lung tissue. On the basis of this finding, the team currently aims to discover small molecules targeting the core of the spliceosome.