Fig. 7

Combination of fimepinostat with standard of care chemotherapy significantly reduces SCLC tumor burden and increases survival in vivo. A Schematic outline of experimental design (B) Representative CT images of RPM mice at time-points following Cre inhalation but before tumor development (Baseline), when tumor was detected, and treatment initiated (Treatment) and when mice reached ethical endpoint (Endpoint). CT images are shown for the fimepinostat alone and fimepinostat/carboplatin/etoposide groups. The area surrounded by the red-dashed line is the heart and the area surrounded by the yellow-dashed line is tumor. Images are representative of at least 8 mice per group. D Representative H&E images and immunohistochemical staining for PCNA are shown. Scale bar = 5 mm in whole lung image and 50 μm in 40X magnification. E The % of PNCA positive cells per tumor area in each tissue section was determined using the automated positive cell detection feature in QuPath for each animal in each cohort (n > 8 mice per cohort). Data is the mean ± S.D for each treatment group. Statistically significant differences were calculated by students t-test (*p < 0.05, ***p < 0.001, ****p < 0.0001). F Kaplan–Meier plot showing that fimepinostat is superior to carboplatin and etoposide treatment and that the combination of fimepinostat (Fim) with carboplatin and etoposide provides a very significant survival advantage in the RPM mouse model of platinum-resistant SCLC (Log-rank Mantel-Cox test, (*p < 0.05, ****p < 0.0001)