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The acquired resistance is driven to some extent by intra-tumor heterogeneity, mainly directed by cancer stem cells (CSCs)
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DNA methyltransferases (DNMT1, DNMT3A, DNMT3B) exhibit differential expression, while ten-eleven translocation methylcytosine dioxygenases (TET1-3) are downregulated in ectopic lesions and eutopic stromal cells, influencing 5-hydroxymethylcytosine levels and epithelial-mesenchymal transition
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