Figure 5 from Adaptive Therapy Exploits Fitness Deficits in Chemotherapy-Resistant Ovarian Cancer to Achieve Long-Term Tumor Control

Competition induces apoptosis in less fit, resistant HGSC cells. A, Cell cycle profiles of OVCAR4 and Ov4Cis cells grown in coculture at a starting ratio of 85:15 OVCAR4:Ov4Cis in low-resource conditions (0.5% FBS exchanged daily). Cells are normalized to the same cell type in monoculture at the same time point. Data are shown as mean ± SD, with n = 3 biological replicates, assessed by a paired t test. P = OVCAR4 compared with Ov4Cis; P = significance between the same cell line in coculture and monoculture at the indicated time point. B and C, OVCAR4 (B) and Ov4Cis (C) cells were grown in low-resource coculture at different starting ratios: 100:0, 90:10, 85:15, 75:25, 50:50, and 0:100 and stained with propidium iodide and Annexin V over time. Cocultures were sorted into green fluorescent (sensitive) and non‐fluorescent (resistant) populations and Annexin V positivity was measured by flow cytometry. Data are shown as mean ± SD, with n = 3 biological replicates, assessed by a one‐way ANOVA compared with 100% control samples. **, P < 0.01; ***, P < 0.001; ****, P < 0.0001. D, OVCAR4 (sensitive; green), Ov4Cis (resistant; red), and OVACR4:Ov4Cis 50:50 cocultures (orange) were grown in low-resource conditions. Every 24 hours, media were exchanged for media that had been preconditioned for 24 hours by either the same cell line (A1 and B1), the other cell line (A2 and B2), or a 50:50 OVCAR4:Ov4Cis coculture (A3 and B3). E, Cell abundance over time (mean ± SD, with n = 3 technical replicates).