INTRODUCTION: Anaplastic lymphoma kinase (ALK), a tyrosine kinase receptor, has 
been initially identified through its involvement in chromosomal translocations 
associated with anaplastic large cell lymphoma. However, recent evidence that 
aberrant ALK activity is also involved in an expanding number of tumor types, 
such as other lymphomas, inflammatory myofibroblastic tumor, neuroblastomas and 
some carcinomas, including non-small cell lung carcinomas, is boosting research 
progress in ALK-targeted therapies.
AREAS COVERED: The first aim of this review is to describe current 
understandings about the ALK tyrosine kinase and its implication in the 
oncogenesis of human cancers as a fusion protein or through mutations. The 
second goal is to discuss its interest as a therapeutic target and to provide a 
review of the literature regarding ALK inhibitors. Mechanisms of acquired 
resistance are also reviewed.
EXPERT OPINION: Several ALK inhibitors have recently been developed, offering 
new treatment options in tumors driven by abnormal ALK signaling. However, as 
observed with other tyrosine kinase inhibitors, resistance has emerged in 
patients treated with these agents. The complexity of mechanisms of acquired 
resistance recently described suggests that other therapeutic options, including 
combination of ALK and other kinases targeted drugs, will be required in the 
future.