A genome-wide CRISPR/Cas9 screen identifies DNA-PK as a sensitiser to <sup>177</sup>Lutetium-DOTA-octreotate radionuclide therapy
Kelly Waldeck, Jessica Van Zuylekom, Carleen Cullinane, Twishi Gulati, Kaylene J. Simpson, Richard W. Tothill, Benjamin J. Blyth, Rodney J. Hicks
Abstract
DDR pathways are critical for sensing and repairing radiation-induced DNA damage, and our study shows that regulation of DDR pathways may be involved in both resistance and sensitivity to PRRT. Additionally, the use of a DNA-PK inhibitor in combination with LuTate PRRT significantly improves the efficacy of the treatment in pre-clinical models, providing further evidence for the clinical efficacy of this combination.
Topics & Concepts
CRISPRGenome editingGene knockoutRadionuclide therapyGeneCas9BiologyGenetic enhancementGeneticsMedicineInternal medicineNeuroendocrine Tumor Research AdvancesLung Cancer Research StudiesNeuroblastoma Research and Treatments