Crizotinib

A human lung adenocarcinoma cell line, A925L, and its highly tumorigenic variant, A925LPE3, with an EML4‐ALK fusion protein (variant 5a, E2:A20)18 were used in this study. All cells were maintained in RPMI‐1640 medium supplemented with 10% FBS, penicillin (100 U/mL), and streptomycin (10 μg/mL) in a humidified CO₂ incubator at 37°C. All cells were passaged for less than 3 months before renewal from frozen early‐passage stocks. Cells were regularly screened for mycoplasma using a MycoAlert Mycoplasma Detection Kit (Lonza, Rockland, ME, USA). Erlotinib, alectinib and ceritinib were obtained from Selleck Chemicals (Houston, TX, USA), crizotinib was obtained from Active Biochem (Hong Kong, China), and cetuximab was obtained from Merck Serono (Darmstadt, Germany), recombinant AREG was obtained from R&D Systems.

The human SCLC cell lines SBC‐3 and SBC‐5, were kindly provided by Dr. K. Kiura (Okayama University, Okayama, Japan). DMS237 and DMS273‐G3H were obtained as reported previously.21 Briefly, DMS273‐G3H was established using tumor cells from a bone metastasis after we had implanted DMS273 orthotopically into the left lung of nude mice. H196 and H1048 were purchased from ATCC (Manassas, VA, USA). DMS114 and DMS454 were purchased from the European Collection of Authenticated Cell Cultures (Porton Down, Hampshire, UK). All cells were maintained in RPMI‐1640 medium supplemented with 10% FBS, penicillin (100 U/mL), and streptomycin (10 μg/mL) in a humidified, 5% CO₂ incubator at 37°C. All cells were passaged for a total of less than 3 months before being replaced by frozen early‐passage stocks. Cells were regularly screened for mycoplasma using a MycoAlert Mycoplasma Detection Kit (Lonza, Rockland, ME, USA). Golvatinib was obtained from Selleck Chemicals (Houston, TX, USA), and crizotinib was obtained from Active Biochem (Kowloon, Hong Kong).