A genome-wide CRISPR/Cas9 screen identifies DNA-PK as a sensitiser to ¹⁷⁷Lutetium-DOTA-octreotate radionuclide therapy.

ABSTRACT: Peptide receptor radionuclide therapy (PRRT) using ¹⁷⁷Lutetium-DOTA-octreotate (LuTate) for neuroendocrine tumours (NET) is now an approved treatment available in many countries, though primary or secondary resistance continue to limit its effectiveness or durability. We hypothesised that a genome-wide CRISPR/Cas9 screen would identify key mediators of response to LuTate and gene targets that might offer opportunities for novel combination therapies for NET patients. Methods: We utilised a genome-wide CRISPR-Cas9 screen in LuTate-treated cells to identify genes that impact on the sensitivity or resistance of cells to LuTate. Hits were validated through single-gene knockout. LuTate-resistant cells were assessed to confirm LuTate uptake and retention, and persistence of som

SUBMITTER: Waldeck K 

PROVIDER: S-EPMC10526672 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature