However, despite these advancements in identifying several proteins associated with acquired drug resistance, the transcriptome and particularly the chromatin dynamics remain largely unexplored, informing our integrative approach to perform deep-sequencing analysis of high HER2 expressing cancer cells (SKBR3) and its lapatinib-resistant counterpart (SKBR3-L) using multi-omics. This evidence concerns the gene ERBB2 and cancer.