Fig. 4
From: Clinical development of targeted and immune based anti-cancer therapies
Mechanism of action of ALK inhibitors. ALK activates various signaling pathways involved in cell proliferation and survival, including the PI3K pathway, the RAS/MEK pathway and the JAK/STAT pathway. ALK inhibitors have similar mechanisms of action by binding to the ATP-binding site and blocking activation of ALK. Crizotinib was the first ALK inhibitor approved by the FDA but, unfortunately, resistance to Crizotinib commonly occurs due to mutations the ALK gene. Therefore, Ceritinib, Alectinib, Brigatinib and Lorlatinib were developed, and can be used for patients who are not responding to Crizotinib