Research on the mechanism by which cancer-associated fibroblasts (CAFs) promote EGFR-TKI resistance in non-small cell lung cancer (NSCLC) via secretory proteins

ABSTRACT: Resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) remains a major clinical challenge in the targeted therapy of non-small cell lung cancer (NSCLC), yet its underlying mechanisms are poorly understood. The tumor microenvironment (TME), which provides a supportive niche for cancer cell survival and progression, plays a pivotal role in NSCLC drug resistance. Our preliminary studies revealed that activated cancer-associated fibroblasts (CAFs) in the TME induce EGFR-TKI resistance in lung cancer cells by secreting neuregulin-1 (NRG1). Further investigations identified STAT3 as a key regulator of CAF activation and secretory function. We thus hypothesize that inhibiting STAT3 activation may block CAF-mediated secretion, thereby reversing EGFR-TKI resistance in lung cancer.

ORGANISM(S): Homo Sapiens

SUBMITTER: Zhe Liu  

PROVIDER: PXD064318 | iProX | Mon May 26 00:00:00 GMT+01:00 2025

REPOSITORIES: iProX