Decoding drug-tolerant persister states in cancer: insights from single-cell, spatial, and computational approaches

Abstract Tyrosine kinase inhibitors (TKIs) have transformed oncogene-driven cancer treatment, but durable responses remain limited by residual disease and acquired resistance. Drug-tolerant persister (DTP) cells represent one therapy-surviving component of minimal residual disease (MRD). This Review examines experimental and computational strategies, including patient-derived xenografts, CRISPR screens, single-cell, spatial, multi-omic and artificial intelligence approaches, to define DTP states, MRD heterogeneity, microenvironmental interactions and clinically actionable vulnerabilities with greater resolution in TKI-treated cancers.