Figure 1.

Tumor heterogeneity contributes to therapeutic resistance, resulting in tumor recurrence and metastasis. Tumor heterogeneity is divided into two subcategories: inter- and intra-tumor heterogeneity. Patient-specific differences (inter-tumor) and variations within the tumor itself (intra-tumor) play a critical role in the patient response to treatment. The basis of heterogeneity arises from alterations in the genome (point mutations, single nucleotide polymorphisms (SNPs), insertions/deletions), transcriptome/proteome (over or under expression of genes, variations in patterns of gene expression), and epigenome (variations in DNA methylation and noncoding RNA regulation patterns, differences in chromatin and histone structure). These levels of heterogeneity are substantiated in the tumor microenvironment (TME), expressed biomarkers, metabolic profile, cell cycle, epithelial–mesenchymal transition (EMT), microcirculation of tumor cells, and presenting clinical pathology. Both concepts of intra- and inter-tumoral heterogeneity must be incorporated into current breast cancer microphysiological system (MPS) models to capture the full landscape of the disease and develop more targeted therapies. Created with Biorender.com (accessed on 5 October 2023).