Fig. 2: Therapeutic response of p16INK4 negative HER2 + BCBM PDX to the combination of tucatinib and abemaciclib.
a Bioluminescence imaging analysis of mice bearing DFBM-355 tumors at indicated weeks after treatment with vehicle control, tucatinib (PO 75 mg/kg, BID), abemaciclib (Abem, PO 75 mg/kg, QD) or tucatinib and abemaciclib combination (Tuca + Abem). Representative bioluminescence images (left panel) and quantification (right panel) of the regions of interest (ROI) in each group of mice at indicated imaging time points. Mean ± SEM. Vehicle control (wk0,2,4, n = 7; wk6, n = 4), Tucatinib (wk0,2, n = 7; wk4, n = 6; wk6, n = 5), Abemaciclib (wk0,2, n = 7; wk4, n = 6; wk6, n = 3) or Tuca + Abem (wk0,2, n = 7; wk4, n = 6; wk6,8,10, n = 5). b Kaplan–Meier survival analysis of mice bearing DFBM-355 treated with vehicle control, tucatinib, abemaciclib, or Tuca + Abem as indicated. n = 7/group. The dotted line indicates the treatment starting time. c IHC analyses of p-RB (control, n = 8 fields; tucatinib, n = 8 fields; abemaciclib, n = 7 fields; Tuca + Abem, n = 8 fields), p-S6RP (control, n = 4 fields; tucatinib, n = 8 fields; abemaciclib, n = 7 fields; Tuca + Abem, n = 9 fields), Ki67 (control, n = 8 fields; tucatinib, n = 8 fields; abemaciclib, n = 7 fields; Tuca + Abem, n = 8 fields) and cleaved Caspase-3 (n = 8 fields/group) of DFBM-355 tumor samples harvested from tumor-bearing mice treated for 4 days with the same drugs at the same doses described in a (Scale bar, 100 μm). d Multiplex immunofluorescence assessment and quantification of change in apoptosis (as measured by pH2Ax) and senescence (as measured by Lamin B1) in DFBM-355. Representative 20x images are shown for each treatment condition. Scale bar, 100 μm. Four whole sections per condition were imaged except for Tuca + Abem where n = 6. For c, d mean ± SD. ns: not significant, One-way ANOVA followed by Dunnett’s multiple comparisons test. Source data are provided as a Source Data file.
