Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 37 (1), 104-122.e12

Treatment-Induced Tumor Dormancy Through YAP-Mediated Transcriptional Reprogramming of the Apoptotic Pathway

Affiliations

Treatment-Induced Tumor Dormancy Through YAP-Mediated Transcriptional Reprogramming of the Apoptotic Pathway

Kari J Kurppa et al. Cancer Cell.

Abstract

Eradicating tumor dormancy that develops following epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment of EGFR-mutant non-small cell lung cancer, is an attractive therapeutic strategy but the mechanisms governing this process are poorly understood. Blockade of ERK1/2 reactivation following EGFR TKI treatment by combined EGFR/MEK inhibition uncovers cells that survive by entering a senescence-like dormant state characterized by high YAP/TEAD activity. YAP/TEAD engage the epithelial-to-mesenchymal transition transcription factor SLUG to directly repress pro-apoptotic BMF, limiting drug-induced apoptosis. Pharmacological co-inhibition of YAP and TEAD, or genetic deletion of YAP1, all deplete dormant cells by enhancing EGFR/MEK inhibition-induced apoptosis. Enhancing the initial efficacy of targeted therapies could ultimately lead to prolonged treatment responses in cancer patients.

Keywords: YAP; dormancy; drug resistance; drug tolerance; epidermal growth factor receptor; lung cancer; senescence.

Similar articles

See all similar articles
Feedback