A study on A549 and H358 cells demonstrated that the inhibitors of PERK (GSK2656157), other UPR-related proteins, heat shock protein 90 (HSP90), and the receptor tyrosine kinase AXL can synergistically enhance the antitumor effects of pemetrexed and trametinib, suggesting a rational combination strategy to treat KRAS-mutant lung cancer. Here, EIF2AK3 is linked to lung cancer.