Figure 3 from Adaptive Therapy Exploits Fitness Deficits in Chemotherapy-Resistant Ovarian Cancer to Achieve Long-Term Tumor Control

Drug-resistant HGSC exhibits reduced proliferative fitness in low-resource conditions. A, Abundance of sensitive (OVCAR4) and resistant (Ov4Cis) cells cocultured over time in high-resource conditions (10% FBS) at a range of starting ratios and passaged every 3 days. Green, OVCAR4; red, Ov4Cis. Data are shown as mean ± SD, with n = 3 technical replicates. B, Ratio of OVCAR4:OV4Cis in A plotted on a log scale over time with start times staggered (so day 0 of the 85:15 ratio experiment is plotted at the time point when there were 85% sensitive cells remaining in the 95:5 starting ratio experiment). The black line shows a linear fit of this log ratio based on the 5:95 dataset (red stars). The slope of the line corresponds to the difference in growth rate between sensitive and resistant cells: gs − gr = g. C, Sensitive OVCAR4 cells (green; left) and resistant Ov4Cis (red; right) cells were grown as monocultures in 0.5% FBS-containing media that were either not changed (A) or exchanged daily with fresh 0.5% FBS-containing media (B). Mean cell abundance is shown over time. D, Abundance of sensitive (OVCAR4) and resistant (Ov4Cis) cells over time when cocultured without passage in low-resource conditions (0.5% FBS exchanged daily) at three starting ratios (85% sensitive, 50% sensitive, and 15% sensitive). Solid lines indicate measured abundance of sensitive (green) and resistant (red) populations over time. Dashed lines indicate predicted cell growth based on their initial seeding density and their measured growth as monocultures. Data are shown as mean ± SD. Model is based on three technical repeat experiments. E, Ratio of OVCAR4:OV4Cis in D plotted on a log scale over time. The black line shows a linear fit of this log ratio based on the 85:15 dataset.