Lineage Tracing Reveals Clone-Specific Responses to Doxorubicin in Triple-Negative Breast Cancer.

ABSTRACT: Triple-negative breast cancer, characterized by aggressive growth and high intratumor heterogeneity, presents a significant clinical challenge. Here, we use a lineage-tracing system, ClonMapper, which couples heritable clonal identifying tags with single-cell RNA-sequencing (scRNA-seq), to better elucidate the response to doxorubicin in a model of TNBC. We demonstrate that, while there is a dose-dependent reduction in overall clonal diversity, there is no pre-existing resistance signature among surviving clones. Separately, we found the existence of two transcriptomically distinct clonal subpopulations that remain through the course of treatment. Among clones persisting across multiple samples we identified divergent phenotypes, suggesting a response to treament independent of clonal ident

SUBMITTER: Morgan D 

PROVIDER: S-EPMC11956957 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature