Cancer cells develop resistance to targeted therapies, and their inherent functional heterogeneity makes it difficult for researchers to understand and characterize these resistance mechanisms. IsoPlexis’ single-cell proteomics is helping researchers overcome resistance to targeted inhibitors, leading to better strategies and combination therapies. In a recent Nature Communications article, James Heath’s team from the California Institute of Technology described using predictive single-cell intracellular proteomics and metabolomics to identify how a cancer cell line transitions to a final drug-resistant state via two distinct trajectories. Using IsoPlexis’ proteomic barcoding technology, the researchers characterized cellular heterogeneity within cell populations at different timepoints and quantitatively connected multiple timepoints to characterize dynamic heterogeneity on an individual cell level. Cellular state changes became prominent around day 3, as most probed analytes exhibited a sharp but transitory increase in variance. Understanding these functional adaptations allowed the team to predict and develop an effective therapeutic combination to overcome this adaptive resistance.