In many patients the underlying cause of drug resistance is unexplained. ALKternate is a clinical trial recruiting pre-treated patients, testing the hypothesis that with fixed alternating TKI therapy, the emergence of ALK resistant clones can be suppressed through applying variable selection pressure compared to continuous treatment with a TKI. This has been tested pre-clinically with a human cell line to complement the clinical trial in progress, ALKternate In this study, ALK TKI treatment was conducted on resistant ALK-rearranged cell lines (methods in Abstract #2074). Protein profiling was performed using the SWATH-MS 2.0 algorithm, conducted on the Sciex 6600 TripleTOF on cell pellets collected prior to treatment and at cycles (C) 5, 11 and 17 of both alternating lorlatinib with crizotinib (ALT) and continual lorlatinib (CONT) treatment arms.This study represents the first of proteomics used to identify resistance mechanisms to ALK TKIs. Data from this in vitro work will inform th..... READ ARTICLE
Journal of Thoracic Oncology DOI:10.1016/j.jtho.2019.08.739
Authors: M. Itchins, A. Hudson, R. Harvie, T. Zaw, M. Mckay, S. Clarke, V. Howell, N. Pavlakis, S. Hayes
