Figure 2.

The downstream ALK activation pathways. ALK is either activated by its ligands pleitrophin, midkin, and FAM150A, or by ALK aberrations. The figure highlights the pathways activated in aberrant ALK, where these pathways also contribute to drug evasion effects. Upon ALK auto-phosphorylation, the RAS/MAPK, PI3K/Akt/mTOR, and JAK/STAT pathways are activated. Signalling through these pathways is correlated with increased cancer cell proliferation, decreased cell apoptosis, metastization, and drug resistance. The interconnection between the RAS/MAPK and PI3K/Akt/mTOR pathways is also indicated.