Target-based screening is a powerful tool if the targeted cancer relies on a specific driver mutation, such as BCR-ABL in chronic myeloid leukemia1 and EML4-ALK in non-small-cell lung cancer2; however, many cancers do not depend on a single mutation or a growth signal and target-based screening resulted in reduced success in discovering anti-cancer drugs due to drug resistance by clonal evolution and alternative growth signal activation in cancer cells3, 4, 5. The gene discussed is EML4; the disease is cancer.