Molecular mechanisms targeting drug-resistance and metastasis in colorectal cancer: Updates and beyond

Figure 1 Major mechanisms of cancer stem cell resistance. Cancer stem cell (CSC) resistance has been associated with CSC characteristics including quiescence, upregulation of ATP-binding cassette transporters, altered drug metabolism, enhanced DNA damage response, and activation of pro survival pathways. The tumor microenvironment (TME) plays a major role in the resistance of CSCs to therapy. CD8 T cells, tumor associated macrophages, and cancer associated fibroblasts (CAFs) are major components of the TME and contribute to tumor progression and metastasis through the secretion of cytokines, growth factors, and angiogenic factors. Additionally, gut microbiota, such as Fusobacterium nucleatum and Enterobacter secrete inflammatory molecules that modulate the TME and contribute to therapy resistance. All of these mechanisms contribute to tumor invasion, angiogenesis, epithelial-to-mesenchymal transition, immunosuppression, drug resistance and survival following treatment. TAMs: Tumor associated macrophages; CAFs: Cancer associated fibroblasts; EMT: Epithelial-to-mesenchymal transition.