Most importantly, screening in vitro cultures derived from BRCA2mutant mouse mammary tumors, cell lines (KB2P1.21, KB2P3.4) and three-dimensional cancer organoids (ORG-KB2P26S.1), using DNA repair-focused shRNA and CRISPR-based libraries, confirmed PARG as a synthetic lethal gene, and loss of this gene represents a major resistance mechanism for PARPi (46). This evidence concerns the gene PARG and cancer.