Research Progress on Therapeutic Targeting of Cancer-Associated Fibroblasts to Tackle Treatment-Resistant NSCLC

Non-small cell lung cancer (NSCLC) accounts for most lung cancer cases and is the leading cause of cancer-related deaths worldwide. Treatment options for lung cancer are no longer limited to surgery, radiotherapy, and chemotherapy, as targeted therapy and immunotherapy offer a new hope for patients. However, drug resistance in chemotherapy and targeted therapy, and the low response rates to immunotherapy remain important challenges. Similar to tumor development, drug resistance occurs because of significant effects exerted by the tumor microenvironment (TME) along with cancer cell mutations. Cancer-associated fibroblasts (CAFs) are a key component of the TME and possess multiple functions, including cross-talking with cancer cells, remodeling of the extracellular matrix (ECM), secretion of various cytokines, and promotion of epithelial-mesenchymal transition, which in turn provide support for the growth, invasion, metastasis, and drug resistance of cancer cells. Therefore, CAFs represent valuable therapeutic targets for lung cancer. Herein, we review the latest progress in the use of CAFs as potential targets and mediators of drug resistance for NSCLC treatment. We explored the role of CAFs on the regulation of the TME and surrounding ECM, with particular emphasis on treatment strategies involving combined CAF targeting within the current framework of cancer treatment.

Automated summary

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and the leading cause of cancer-related deaths worldwide. Targeted therapy and immunotherapy have emerged as promising treatment options for NSCLC, but drug resistance and low response rates still pose significant challenges. Cancer-associated fibroblasts (CAFs) play a crucial role in the tumor microenvironment, promoting cancer cell growth, invasion, metastasis, and drug resistance. Targeting CAFs could be a valuable strategy for NSCLC treatment.