Cracking the Code of Resistance across Multiple Lines of ALK Inhibitor Therapy in Lung Cancer.

In the setting of recent exciting clinical results and numerous ongoing trials, Gainor and colleagues explored mechanisms of acquired resistance to first- and second-generation ALK inhibitors in ALK-rearranged non-small cell lung cancer and found that an increased frequency and distinct spectrums of resistance mutations emerged with the more potent second-generation inhibitors. Their findings have important and immediate clinical implications as the resistance mutations detected impart differential sensitivities to available ALK inhibitors, thereby highlighting the need for sequential biopsies with molecular testing to determine the most effective treatment strategy upon disease progression. Cancer Discov; 6(10); 1084-6. ©2016 AACRSee related article by Gainor et al., p. 1118. ©2016 American Association for Cancer Research.