In a 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 keeping with the hypothesis, the genetic profiles identified demonstrate the emergence of different clones over time and between treatment strategies. This supports further investigation into the novel strategy of alternating therapy as planned in the ALKternate trial.
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Journal of Thoracic Oncology DOI:10.1016/j.jtho.2019.08.844
Authors: M. Itchins, A. Hudson, S. Hayes, R. Harvie, G.H. Wei, M. Buckland, S. Clarke, V. Howell, N. Pavlakis