ALK and neoplasm: Lastly, although ALK-resistant mutations and mesenchymal tumor cells can coexist in a single crizotinib-resistant lesion, the ALK-resistant mutation is largely restricted to epithelial-type tumor cells, whereas tumor cells with the mesenchymal phenotype can exhibit cross-resistance to crizotinib and new-generation ALK–TKIs, including alectinib, ceritinib, and lorlatinib [36].