Abstract
ALK (anaplastic lymphoma kinase) inhibitors are approved in for ALK gene rearrangement positive (ALK+) lung cancer, but resistance remains a challenge. We discovered that RAS-RAF-MEK-ERK signaling controls the ALK inhibitor response in ALK+ lung cancer and is critical for ALK inhibitor resistance. Upfront ALK-MEK inhibitor polytherapy may enhance response and forestall resistance.