1.3. Cancer-associated fibroblasts (CAFs):
Non-malignant stromal cells in the tumor microenvironment are crucial
for drug resistance and tumor progression [112]. Stromal cells are
polarized by their interaction with tumor cells, and through education
of tumor cells, they secrete diverse molecules, resulting in
pharmacokinetics regulation, immunosuppression, and metabolic
regulation, subsequently, they reduce therapeutic outcomes [112].
The most common type of stromal cells are CAFs. CAFs by involvement in
ECM remodeling and metabolic reprogramming, as well as by secretion of
diverse factors such as cytokines (IL-6, IL-8, IL-10, etc.), growth
factors (hepatocyte growth factor, stromal cell-derived factor,
fibroblast growth factor, transforming growth factor), various
chemokines, metabolites, and exosomes (contain lncRNAs, miRNAs and
mitochondrial DNA (mtDNA)) which activate multiple signaling cascades,
cause drug resistance, and ultimately tumor recurrence [111, 112,
120].