2023
DOI: 10.1101/2023.04.04.535588
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Single cell lineage tracing reveals clonal dynamics of anti-EGFR therapy resistance in triple negative breast cancer

Abstract: Although many primary triple negative breast cancers (TNBCs) have enhanced expression of epidermal growth factor receptor (EGFR), EGFR-targeted therapies have shown only variable and unpredictable clinical responses in TNBCs. Here we integrate cellular barcoding and single-cell transcriptomics methods to comprehensively characterize the subclonal dynamics of adaptation of TNBC cells in response to afatinib, tyrosine kinase inhibitor (TKI) that irreversibly inhibits EGFR. Integrated lineage tracing analysis on … Show more

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Cited by 1 publication
(9 citation statements)
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“…Interestingly, the most overrepresented classes among the drugs predicted to selectively inhibit the afatinib-tolerant subpopulation were IGF1R, HDAC, and AKT/MTOR/PI3K inhibitors (Figure 3H). We have already shown that afatinib and IGF1R inhibitors have a strong synergistic effect on these cells (4), thus validating the DREEP predictions that IGF1R inhibitors should deplete the cell population that do not respond to afatinib in this cell line.…”
Section: Resultssupporting
confidence: 80%
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“…Interestingly, the most overrepresented classes among the drugs predicted to selectively inhibit the afatinib-tolerant subpopulation were IGF1R, HDAC, and AKT/MTOR/PI3K inhibitors (Figure 3H). We have already shown that afatinib and IGF1R inhibitors have a strong synergistic effect on these cells (4), thus validating the DREEP predictions that IGF1R inhibitors should deplete the cell population that do not respond to afatinib in this cell line.…”
Section: Resultssupporting
confidence: 80%
“…A positive or negative score means that the cell is predicted to be resistant or sensitive to bortezomib, respectively. ( F ) UMAP plot of 1,541 MDA-MB-468 cells from Pellecchia et al (4). Cells are colour-coded according to whether they belong to an afatinib-sensitive or tolerant lineage.…”
Section: Resultsmentioning
confidence: 99%
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