(A) Cell Titer Glo assay of CD437 10-point DRC for parental cell line and CD437-resistant clones A, B, C, and D. Data are represented as mean ± SD. (B) Table showing EC50 for CD437 from parental A673-M1 and each CD437-resistant clone. POLA1 mutations reported for each resistant clone. (C) Cell Titer Glo assay of CD437 10-point DRC for parental cell line and clones A, B, C, D, E, F, G, H, I and J. Data are represented as mean ± SD. (D) Table showing EC50 for CD437 from parental 319-N1-Cl31 and each CD437-resistant clone. Polal mutations detected in each resistant clone. (E) Sequencing trace for I768S mutation found in Pola1 from mSCLC clone A. (F) Crystal structure of POLA1 (Protein Data Bank accession 5IUD). Mutated codons found in CD437-resistant clones from Ewing sarcoma and mSCLC (red). See also Figure S3 C–D.