1. Oncogenic ALK signaling.
Oncogenic ALK signaling. The ALK fusion protein is constitutively active and signals via phospholipase Cγ (PLCγ), JAK–STAT, RAS–RAF–MEK–ERK, and PI3K–AKT–mTOR pathways (13). This signaling results in the aberrant regulation of a number of genes (some of which are represented here), ultimately driving cell-cycle progression, survival, proliferation, and angiogenesis (50). Secondary mutations in the ALK kinase domain (starred) cause acquired resistance to ALK TKIs. Several of the bypass signaling tracks implicated in ALK TKI resistance are also shown here—EGFR, HER2/HER3, MET, KIT, and IGF1R with their respective ligands.
Jessica J. Lin et al. Cancer Discov 2017;7:
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