Although epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors elicit dramatic initial effects in EGFR-mutant non-small-cell lung cancer (NSCLC), drug resistance commonly develops. Shah et al. modelled acquired resistance in EGFR-mutant lung adenocarcinoma cells, and found that Aurora kinase inhibitors synergistically inhibited cancer cell growth in combination with EGFR inhibitors; findings that were confirmed in mouse and patient-derived xenograft models. In vitro, activation of Aurora kinase A, by its coactivator TPX2, was necessary for acquired resistance and mitigated apoptosis. TPX2 levels were increased in patients with EGFR-mutant NSCLC who had developed erlotinib resistance.
Shah, K. et al. Aurora kinase A drives the evolution of resistance to third-generation EGFR inhibitors in lung cancer. Nat. Med. https://doi.org/10.1038/s41591-018-0264-7 (2018).
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Crunkhorn, S. Combating resistance to EGFR inhibitors. Nat Rev Drug Discov 18, 18 (2019). https://doi.org/10.1038/nrd.2018.232