Schematic reveals fitness costs of resistance in chemotherapy-resistant ovarian cancer, suggesting adaptive therapy can enhance long-term control.
Fitness costs of resistance are observed in vivo. A, Schematic depicting in vivo coculture experiments. B, qPCR of GFP and RFP DNA in subcutaneous coculture tumors (OVCAR4:Ov4Cis, 0:100, 10:90, 50:50, 80:20, and 100:0). Tumors were harvested after 12 weeks and qPCR for GFP and RFP is plotted against a standard curve of input DNA (see Supplementary Fig. S7). Solid line, mean; dashed line, SD, one icon per tumor; and n = 2 to 4 tumors per starting ratio. C, IHC for p53, GFP, and cleaved caspase‐3 in 50:50 OVCAR4:Ov4Cis tumors harvested from different mice at weeks 4 and 12. Representative slides are shown at low (top) and high (bottom) magnification. Arrows indicate p53+, GFP-negative resistant cells. Circles, cleaved caspase-3–positive resistant cells; squares, cleaved caspase-3–negative resistant cells. D, Pixel quantification of sensitive and resistant cells. Data are shown as mean ± SD, with n = 2 mice per time point. Solid line indicates the starting ratio of S:R cells.
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