| First Author | Kurppa KJ | Year | 2020 |
| Journal | Cancer Cell | Volume | 37 |
| Issue | 1 | Pages | 104-122.e12 |
| PubMed ID | 31935369 | Mgi Jnum | J:283659 |
| Mgi Id | MGI:6386880 | Doi | 10.1016/j.ccell.2019.12.006 |
| Citation | Kurppa KJ, et al. (2020) Treatment-Induced Tumor Dormancy through YAP-Mediated Transcriptional Reprogramming of the Apoptotic Pathway. Cancer Cell 37(1):104-122.e12 |
| abstractText | 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. |
