Cancer-associated fibroblasts derived from EGFR-TKI-resistant tumors reverse EGFR pathway inhibition by EGFR-TKIs.

ABSTRACT: Epidermal growth factor receptor (EGFR) plays a critical role in oncogenesis, which makes it an attractive target for pharmacologic inhibition. Yet, EGFR inhibition with tyrosine kinase inhibitors (TKI) does not result in a measurable and sustainable clinical benefit in a vast majority of tumors. This emphasizes the need for further investigations into resistance mechanisms against EGFR-TKIs. We previously reported the generation of an in vivo adenocarcinoma model of EGFR-TKI-acquired resistance that was devoid of the known mechanisms of resistance. Using this same xenograft model, we now show that the tumor stroma plays an important role in limiting responsiveness to EGFR-TKIs. EGFR-TKI-resistant tumors display increased surface expression of CD44(hi)/CD24(lo) and markers of epithelial to

SUBMITTER: Mink SR 

PROVIDER: S-EPMC2891820 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature