Abstract

Quantitative metrics to objectively assess the fidelity of cancer models, such as cell lines, organoids, or patient-derived xenografts (PDXs), remain elusive, with histological criteria or the presence of specific mutations often used as driving principles. We show that molecular criteria, based on the regulatory proteins responsible for maintaining transcriptional cell state and its regulatory network, are effective in identifying models that can recapitulate drug mechanism of action and drug sensitivity, independent of histological consideration.