Role of cancer-associated fibroblasts in the resistance to antitumor therapy, and their potential therapeutic mechanisms in non-small cell lung cancer

Non-small cell lung cancer (NSCLC) is a malignant tumor with high morbidity and mortality rates, which seriously endangers human health. Although treatment methods continue to evolve, the emergence of drug resistance is inevitable and seriously hinders the treatment of NSCLC. The tumor microenvironment (TME) protects tumor cells from the effects of chemotherapeutic drugs, which can lead to drug resistance. Cancer-associated fibroblasts (CAFs) are an important component of the TME, and various studies have demonstrated that CAFs play a crucial role in drug resistance in NSCLC. However, the drug resistance mechanism of CAFs and whether CAFs can be used as a target to reverse the resistance of tumor cells remain unclear. The present review discusses this issue and describes the heterogeneity of CAF markers, as well as their origins and resident organs, and the role and mechanism of this heterogeneity in NSCLC progression. Furthermore, the mechanism of CAF-mediated NSCLC resistance to chemotherapy, targeted therapy and immunotherapy is introduced, and strategies to reverse this resistance are described.