Clonal dynamics shaped by diverse drug-tolerant persister states in melanoma resistance.

ABSTRACT: Most advanced melanomas initially respond to targeted therapy but eventually relapse. Rather than acquiring new mutations, resistance is driven by drug-tolerant persister cells that enter a reversible drug-refractory state. We developed MeRLin, a high-resolution lineage tracing platform integrating cellular barcoding, single-cell transcriptomics, RNA fluorescence in situ hybridization (FISH), and computational analyses to track clonal and transcriptional dynamics in patient-derived melanoma models during prolonged therapy. Clonal dynamics revealed that persister subpopulations first responded to treatment but persisted and expanded during minimal residual disease, ultimately leading to tumor recurrence. Pre-treatment melanoma populations diversified into four conserved persister states cha

SUBMITTER: Li H 

PROVIDER: S-EPMC12458950 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature