Journal: Bladder Cancer
Article Title: Impact of DNA repair deficiency on sensitivity to antibody-drug conjugate (ADC) payloads in bladder cancer *
doi: 10.1177/23523735251317865
Figure Lengend Snippet: Combined activity of MMAE and SN-38 with DNA repair inhibitors. (a) Cytotoxic activity of combining MMAE or SN-38 with ATR inhibition (berzosertib, BERZ), USP1 inhibition (ML323), or PARP inhibition (Olaparib, OLA; talazoparib, TALA) in KU19-19 (top graph) and J82 (bottom graph) bladder cancer cell lines with versus without HR deficiency conferred by BRCA2 depletion. (b) Cytotoxic activity of combining MMAE or SN-38 with ATR inhibition (berzosertib, BERZ), USP1 inhibition (ML323), or PARP inhibition (Olaparib, OLA; talazoparib, TALA) in NER-proficient ( ERCC2 WT) KU19-19 cells versus NER-deficient ( ERCC2 -mutant) KE182 cells (top graph) or NER-proficient (ERCC4 WT) H460 cells versus NER-deficient (ERCC4-deleted) H460 cells (bottom graph). Combination activity is quantified by the combination index (CI, see Methods) with positive log10(CI) values indicative of antagonism and negative log10(CI) values indicative of synergism. HRP, homologous recombination proficient (WT BRCA2); HRD, homologous recombination deficient (BRCA2 depleted); NERP, nucleotide excision repair proficient; NERD, nucleotide excision repair deficient. Error bars represent standard deviation of data collected from assays performed in quadruplicate.
Article Snippet: Human bladder cancer cell lines J82 and KU19-19 were purchased from ATCC and DSMZ, respectively.
Techniques: Activity Assay, Inhibition, Mutagenesis, Homologous Recombination, Standard Deviation