Targeting the RET tyrosine kinase in neuroblastoma: A review and application of a novel selective drug design strategy.

The RET (REarranged during Transfection) gene, which encodes for a transmembrane receptor tyrosine kinase, is an established oncogene associated with the etiology and progression of multiple types of cancer. Oncogenic RET mutations and rearrangements resulting in gene fusions have been identified in many adult cancers, including medullary and papillary thyroid cancers, lung adenocarcinomas, colon and breast cancers, and many others. While genetic RET aberrations are much less common in pediatric solid tumors, increased RET expression has been shown to be associated with poor prognosis in children with solid tumors such as neuroblastoma, prompting an interest in RET inhibition as a form of therapy for these children.