CRISPR genome-wide synthetic lethality screens of KRAS-driven mouse pancreatic ductal adenocarcinoma cells

We performed CRISPR genome-wide synthetic lethality screens to identify genetic vulnerabilities and chemogenetic interactions in KRAS-driven pancreatic cancer. We identify ERAD as a genetic target that synergizes with FTS treatment and we show that FTS treatment induces ER stress, which was further enhanced by inhibition of ERAD, leading to synergistic induction of apoptosis in pancreatic tumor cells. Altogether, our screens enable us to identify combination therapies for cancer treatment. Overall design: Screens were performed using the 4292 doxycycline-inducible Kras-G12D pancreatic ductal adenocarcinoma cell line in duplicate with two independent viral infections. Please note that, on Nov 29, 2021, 1) The fastq files (for samples RA, RB, FA, FB) have been replaced as they were trimmed via cutadapt. The updated files are raw files before any processing 2) The *counts.txt files (for samples RA, RB, FA, FB) have been replaced as the original ones had some minor formatting issues with line breaks 3) Additional samples (samples GA, GB, KA, KB) have been added.