Figure 1.

Mechanisms of TME-driven chemoresistance promoted by p53 loss. Tumor tissue-level chemoresistance is the result of complex interactions between cancer cells and their TME, with p53 acting as a key regulator. Functional loss of normal p53 can happen in tumor-associated stromal cells, such as fibroblasts, epithelial cells and tissue-resident cells, which cooperates with GOF p53 mutations in cancer cells to enforce a chemoresistant microenvironment, while also augmenting resistant and invasive phenotypes. CAF, cancer-associated fibroblast; ECM, extracellular matrix; EMT, epithelial-to-mesenchymal transition; IL-6, interleukin-6; IL-8, interleukin-8; mutp53, mutant p53; SASP, senescence-associated secretory phenotype; TME, tumor microenvironment; VEGF, vascular endothelial growth factor; wtp53, wild-type p53.