Fig. 6: Resistance to broad DDA in SLFN11 absent/low cancers (different cancer types) can be overcome by inhibition of ATR, WEE1 or CHK1.
From: SLFN11 informs on standard of care and novel treatments in a wide range of cancer models
a HSA synergy scores of the indicated combinations in SLFN11 high and low pancreatic cancer cell lines. Data are presented as medians with interquartile range (Wilcoxon test). *P < 0.05. b Log IC50 values of cell lines from the indicated cancers following treatments with gemcitabine (GDSC003 dataset) or gemcitabine/ATRi (additional screen, caveat). Data are presented as means ± s.d. *P < 0.05; ****P < 0.0001; ns not significant (one-way ANOVA with Dunnett’s T3 multiple comparisons test). The dashed lines indicate the maximum concentrations of gemcitabine or gemcitabine/ATRi used in the screen. Miscellaneous upper gastrointestinal cancer: HNSC head and neck squamous cell carcinoma, ESCA oesophageal carcinoma. Miscellaneous genitourinary cancer: PRAD prostate adenocarcinoma, BLCA bladder urothelial carcinoma, UCEC uterine corpus endometrial carcinoma, OV ovarian serous cystadenocarcinoma. c Scatter plots of SLFN11 low and high pan-cancer cell lines following 72-h combination treatments. The solid horizontal line indicates the threshold for the maximum activity of the combination and the dashed line the excess effect over the highest single agent (HSA). The black colour indicates cell lines that pass both thresholds and benefit from the combination treatment (indicated as percentages of total cell lines evaluated in the plots). P values derive from a two-sided Fisher’s exact test as further described in the “Methods”. SRA737 is the CHK1i in the left plot.
