In this era of more rational therapies, substantial efforts are being made to 
identify optimal targets. The discovery of translocations involving the 
anaplastic lymphoma kinase (ALK) receptor tyrosine kinase in a subset of 
non-small cell lung cancers has become a paradigm for precision medicine. 
Notably, ALK was initially discovered as the fusion gene in anaplastic large 
cell non-Hodgkin lymphoma, a disease predominantly of childhood. The discovery 
of activating kinase domain mutations of the full-length ALK receptor as the 
major cause of hereditary neuroblastoma, and that somatically acquired mutations 
and amplification events often drive the malignant process in a subset of 
sporadic tumors, has established ALK as a tractable molecular target across 
histologically diverse tumors in which ALK is a critical mediator of 
oncogenesis. We are now uncovering the reexpression of this developmentally 
regulated protein in a broader subset of pediatric cancers, providing 
therapeutic targeting opportunities for diseases with shared molecular etiology. 
This review focuses on the role of ALK in pediatric malignancies, alongside the 
prospects and challenges associated with the development of effective 
ALK-inhibition strategies.