3 years ago

ALK and IGF-1R as independent targets in crizotinib resistant lung cancer

Christabel Wilson, John C. Ashton, Mhairi Nimick, Hayley Nehoff
ALK positive non-small cell lung cancer is highly responsive to ALK inhibitors such as crizotinib, but drug resistance typically develops within a year of treatment. In this study we investigated whether IGF-1R is an independent druggable target in ALK-positive lung cancer cells. We confirmed that combination ALK and IGF-1R inhibitor treatment is synergistically cytotoxic to ALK-positive lung cancer cells and that this remains the case for at least 12 days after initial exposure to crizotinib. ALK-positive cells with acquired resistance to crizotinib did not acquire cross-resistance to IGF-1R inhibition, though combination treatment in the resistant cells gave additive rather than synergistic cytotoxicity. We concluded that IGF-1R is an independent druggable target in ALK-positive lung cancer and support the trial of combination treatment.

Publisher URL: https://www.nature.com/articles/s41598-017-14289-w

DOI: 10.1038/s41598-017-14289-w

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