Investigating therapy-induced senescence as a reversible escape mechanism of drug resistance in breast cancer cells using high-dose doxorubicin treatment

The emergence of drug resistance remains a critical challenge in cancer treatment, significantly contributing to high mortality rates. Here, we investigate therapy-induced senescence (TIS) as a reversible escape mechanism of drug resistance in breast cancer cells. Using high-dose doxorubicin, we induced TIS in MCF7 and T47D breast cancer cell lines. scRNA sequencing revealed a unique transcriptomic profile for TIS cells, distinct from both parental and repopulated cells in every cell line, exposing a small subpopulation of TIS cells with the potential to escape senescence. Gene set enrichment analysis indicated significant downregulation of proliferation-related genes, downregulation of DNA repair pathways, and the upregulation of immune response related genes.