... Using RNA sequencing, we show a clear evolutionary path from drug-sensitive parental cells to drug-tolerant persisters and long-term derived drug-acquired resistant cells. We are currently profiling vulnerabilities of drug-tolerant EGFR-mutant and EML4-ALK fusion persisters using genetic and pharmacologic approaches. In conclusion, YAP activation is a functional marker of EGFR-mutant and EML4-ALK fusion persisters derived under high-dose drug treatment with third-generation TKIs. Targeting YAP activation either on the level of upstream signaling input, its relocalization between cytoplasm and nucleus, or its action as transcriptional coactivator may represent a promising combinatorial treatment approach to limit resistance development and improve patient survival in lung adenocarcinoma. READ ARTICLE
Journal of Thoracic Oncology DOI:10.1016/j.jtho.2019.12.070
Authors: F. Haderk, C. Fernández-Méndez, K. N. Shah, W. Wu, J. Guan, J. Rotow, D. Allegakoen, V. Olivas, S. Bandyopadhyay, C. Kuo, T. Bivona