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Single cell lineage tracing reveals clonal dynamics of anti-EGFR therapy resistance in triple negative breast cancer

GSE228154 Homo sapiens Expression profiling by high throughput sequencing 5 samples Submitted 2024/03/25 Platform GPL24676
Summary
We investigate non-genomic mechanisms determining cellular response to EGFR inhibitors in triple negative breast cancer (TNBC). We integrate methods for cellular barcoding and single-cell transcriptomics to enable cell lineage tracing and explore the subclonal evolution of adaptation in an established preclinical model of TNBC in response to incremental concentrations of Afatinib, a second generation EGFR-TKI that irreversibly inhibits both EGFR and HER2. Retrospective lineage tracing data analysis uncovered a pre-existing subpopulation of rare Afatinib-tolerant cells displaying distinct biological features, such as elevated mRNA levels of the IGFBP2 gene. Furthermore, we investigated temporal coordination of transcriptional programs in drug resistant clones with high replication fitness by reordering cells along a pseudotime trajectory. Interestingly, it revealed the activation of biological processes, such as fatty acid metabolism, which have previously been linked to EGFR-TKIs resistance mechanisms.
Published in
Single cell lineage tracing reveals clonal dynamics of anti-EGFR therapy resistance in triple negative breast cancer
Pellecchia S, Franchini M, Viscido G et al. · Genome medicine 2024 · PMID 38605363 · doi:10.1186/s13073-024-01327-2
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Also filed as BioProject PRJNA948402 and SRA study SRP429142. Searching any of these in the dataset finder brings you back here.

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