Expanding the portfolio of anaplastic lymphoma kinase inhibitors for anaplastic lymphoma kinase-rearranged lung cancers

The discovery of molecular targets has led to a paradigm shift in the treatment of patients with lung cancer. Approximately 3% to 7% of the NSCLC patients harbor a rearrangement in the anaplastic lymphoma kinase (ALK) gene. The N-terminal portion of EML4 inverts and fuses to the intracellular, tyrosine kinase domain-containing region of ALK, forming the most common ALK rearrangement (1). Other, rarer upstream fusion partners for ALK (e.g., KIF5B and TFG) have also been reported in non–small-cell lung cancers. There is substantial evidence that these alterations are events that are acquired early in tumorigenesis. ALK rearrangements are commonly found in patients who present with distinct clinicopathological features including younger age, never or former light smoking history, adenocarcinoma histology, and signet ring or acinar subtypes; there is no clear association with race and sex. Even though ALK rearrangement is more common in lung adenocarcinoma, and also identified in large cell carcinoma and NSCLC-NOS (not otherwise specified), testing for these fusions should be considered even in patients with squamous cell and mixed histologies, or those with small biopsy samples.