An ALK inhibitor collapses the population in days. What regrows is not a mutant that was waiting there.
The population. Cells are shaded by their starting state. When the drug kills them, survivors are drawn at random — nothing about a cell's starting state decides whether it lives. That is the measured result: across 2,993 barcoded lineages, day-0 state predicted survival at AUC 0.506, which is chance.
The space. Twelve hallmark programmes describe a cell's state. Three axes hold 90% of the variation between the drug classes and states shown, which is why this can be drawn in 3D at all.
The arrows. Each class moves the cell by its measured average displacement across 720,216 compound signatures. The number quoted for each class is its alignment with the chronic resistant state, measured in gene space — not read off this picture.
Stacking drugs adds the vectors. Real combinations do not behave that way: we tested it across 801 drug pairs and the rule failed.
Hypothesis generation on public data. Not a clinical result.