E-Mail IMAGE: Graphical schema showing the mechanism for overcoming intrinsic resistance to ALK-TKIs owing toTP53 mutations view more Credit: Kanazawa University Most lung cancers are of a type called non-small-cell lung carcinoma (NSCLC). This type of cancer is relatively insensitive to chemotherapy, so NSCLC therapies are usually based on drug treatment. Alectinib is a drug commonly used for treating patients with NSCLC. It addresses a gene rearrangement known as ALK that occurs in 3 to 5% of NSCLC patients (alectinib belongs to a class of drugs called ALK tyrosine kinase inhibitors). It has been unclear, however, whether there is a correlation between the use of alectinib and the poorer prognosis in ALK-NSCLC patients in which secondary cancer mutations are observed -- the latter are known to occur with a frequency of about 25%. Now, Azusa Tanimoto from Kanazawa University and colleagues have investigated this correlation. They found that such secondary mutations reduce the efficacy of alectinib, but they also suggest how to overcome this issue.