UBA1 is an essential, highly expressed gene target in SCLC. A, Box and whisker plot of UBA1 (top) and UBA6 (bottom, representative control gene) dependency (CERES) scores by cancer subtype (n = 20). Colored boxes indicate disease site (n = 11). CERES scores of 0 and -1 represent the median pan-cancer nonessential and essential gene scores, respectively. A nonparametric Wilcoxon signed-rank test revealed that the median UBA1 CERES score across all cancer cell lines evaluated (n = 423) was significantly different from the median CERES score for nonessential cancer genes of 0. B, Box and whisker plot displaying relative UBA1 mRNA expression across cancer cell lines (SCLC n = 50; colorectal n = 56; neuroblastoma n = 16; AML n = 36; NSCLC n = 128) and immortalized normal cell lines (n = 6) using a log-arithmic (log10) scale. A Student t test revealed UBA1 expression was high in SCLC cell lines compared with other cancer subtypes. Normal cell lines originated from ovarian, breast, fibroblast, kidney, lung, and prostate tissues. Blue asterisks represent the immortalized normal lung cell lines evaluated. C, Dose response curves of SCLC cell lines after treatment with TAK-243 for 3 days, with individual EC50 indicated in the legend. Individual points on the plots indicate the mean of three technical replicates with SD represented by error bars. Outliers were excluded from analysis. Colors represent sensitive (red-yellow) and resistant (green) SCLC cell lines. GI, gastrointestinal; AML, acute myeloid leukemia; SCLC, small cell lung cancer; NSCLC, non small cell lung cancer.