ve-821 and olaparib

Up to 40% of lung adenocarcinoma have been reported to lack ataxia-telangiectasia mutated (ATM) protein expression. We asked whether ATM-deficient lung cancer cell lines are sensitive to poly-ADP ribose polymerase (PARP) inhibitors and determined the mechanism of action of olaparib in ATM-deficient A549 cells.. We analysed drug sensitivity data for olaparib and talazoparib in lung adenocarcinoma cell lines from the Genomics of Drug Sensitivity in Cancer (GDSC) project. We deleted ATM from A549 lung adenocarcinoma cells using CRISPR/Cas9 and determined the effects of olaparib and the ATM/Rad3-related (ATR) inhibitor VE-821 on cell viability.. IC. Patients with tumours characterised by ATM-deficiency may benefit from treatment with a PARP inhibitor in combination with an ATR inhibitor.

Topics: Adenocarcinoma; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Ataxia Telangiectasia Mutated Proteins; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Clustered Regularly Interspaced Short Palindromic Repeats; Gene Deletion; Histones; Humans; Lung Neoplasms; Mutation; Nitroso Compounds; Phosphorylation; Phthalazines; Piperazines; Poly(ADP-ribose) Polymerase Inhibitors; Pyrazines; Pyrimidines; RNA, Messenger; Sulfones; Tumor Suppressor Protein p53