New Drug May Overcome Resistance to Xalkori

The drug crizotinib (Xalkori) is used to treat non-small cell lung cancer (NSCLC) with mutations in the ALK gene. However, most patients develop resistance to the drug, usually because of further mutations in the ALK gene. A new ALK inhibitor drug, PF-06463922, may offer a solution. PF-06463922 blocked a variety of Xalkori-resistant mutant versions of ALK in cell cultures, and inhibited the growth of Xalkori-resistant ALK-mutant tumors in mice. PF-06463922 also combated tumor cells driven by mutations in ROS1, a gene closely related to ALK, in mouse models. Like Xalkori, PF-06463922 may therefore also be effective for NSCLC patients with ROS1 mutations. Finally, PF-06463922 was able to penetrate into the brain in multiple animal species–important because lung cancer often spreads to the brain.