Role of Cancer-Associated Fibroblast in Gastric Cancer Progression and Resistance to Treatments

Abstract

Although the survival of gastric cancer (GC) patients has gradually improved, the outcomes of advanced GC patients remain unsatisfactory despite standard treatment with conventional chemotherapy or targeted agents. Several studies have shown that cancer-associated fibroblasts (CAFs), a major component of tumor stroma in GC, may have significant roles in GC progression and resistance to treatments. CAFs are a major source of various secreted molecules in the tumor microenvironment, which stimulate cancer cells and other noncancerous components of GC. Surprisingly, these factors could be involved in gastric carcinogenesis. Cytokines, including interleukin-6 and interleukin-11, or growth factors, such as fibroblast growth factor produced from CAFs, can directly activate GC cells and consequently lead to the development of an aggressive phenotype. Galectin-1 or hepatocyte growth factor can be involved in CAF-derived neovascularization in GC. In addition, recent studies showed that CAFs can affect tumor immunity through M2 polarization of tumor-associated macrophages. Finally, the current study aimed to introduce several inhibitory agents and evaluate their suppressive effects on CAFs in patients with GC progression. However, further studies are required to evaluate their safety and select appropriate patients for application in clinical settings.