eLife Assessment
This valuable study uses single-cell profiling, lineage barcoding, and functional assays to examine drug-tolerant persisters in a BRAF-inhibited melanoma cell line. The data provide solid evidence that persisters arise from many lineages and have altered calcium handling and increased sensitivity to ferroptosis, although the lineage result is difficult to interpret without knowing how many cells survived treatment. The broader claim that these cells represent substates within a single persister state is less well supported, as it rests largely on transcriptomic projections, lacks time-resolved data, and has been examined in only one cell line.