Molecular interrogation revealed biomarker-defined classes of responsive models including: (a) RB1/TP53 loss of function and associated replication stress observed predominantly in SCNPC and in some highly aggressive adenocarcinomas, (b) SLFN11 expression observed in a subset of RB1 WT/TP53 altered adenocarcinomas, and (c) specific DNA repair mutations (including ATR and CHD1) that impact PBD-initiated DNA damage. Here, CHD1 is linked to adenocarcinoma.