PARPi resistance screening in KB2P-3.4 2D cell lines. PARPi resistance screens in BRCA2-deficient cells

BRCA1 and BRCA2 both function in DNA double-strand break repair by homologous recombination (HR). Due to their HR defect, BRCA1/2-deficient cancers are sensitive to poly(ADP-ribose) polymerase inhibitors (PARPi) but they eventually acquire resistance. Preclinical studies yielded several PARPi resistance mechanisms that do not involve BRCA1/2 reactivation, but their relevance in the clinic remains elusive. To investigate which BRCA1/2-independent mechanisms drive spontaneous resistance in vivo, we performed several loss-of-function screens targetting both the Whole Genome and selected lists of DNA Damage Repair (DDR) genes.