Abstract A091: Targeting homologous recombination repair defects in lung cancer

Abstract

Non-Small Cell Lung Cancer (NSCLC) is the leading cause of cancer related mortality worldwide, and accounts for 80-85% of all lung cancer diagnoses. While targeted therapies against epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) fusions have proven to be effective for the treatment of NSCLC, only a fraction of NSCLC patients (i.e. 70%). Amongst the PDX models containing a biallelic HRR mutation (ATM, BAP1, RAD51D & XRCC2), only ATM biallelic mutant models were sensitive to niraparib (2 out of 6). Furthermore, none of the of nine monoallelic mutant models (ATM, ATR, BRCA1/2, RAD50 & RAD52) were sensitive to niraparib. Surprisingly, 7.5% (3 out of 40) of the HRR WT PDX models were sensitive to niraparib. Further analysis is required to elucidate the molecular mechanisms driving niraparib sensitivity in HRR WT NSCLC. Citation Format: Asli Muvaffak, Yinghui Zhou, Bin Feng, Sarah Wang, Jing Ju Wang, Sridhar Ramaswamy, Kevin G Coleman. Targeting homologous recombination repair defects in lung cancer [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr A091. doi:10.1158/1535-7163.TARG-19-A091