Neuroblastoma: Essential genetic pathways and current therapeutic options

Neuroblastoma is a very diverse pediatric tumor that starts from the neural crest, and it is responsible over more than 15% of all juvenile cancer deaths. Clinical signs and symptoms are highly dependent on tumor origin and spread. Bone, lymph nodes, liver, intracranial and orbital tissues, lungs, and the central nervous system are frequently involved in metastatic neuroblastoma. Neuroblastoma enhances with contrast in Computed Tomography (CT) scans as a solid heterogeneous mass which might invade to adjacent ipsilateral or contralateral lymph nodes, tissues, and vessels. Whereas the Magnetic Resonance Imaging (MRI) acquires an acceptable diagnostic accuracy for detection of spinal cord and musculoskeletal metastases. Lorlatinib, a novel ALK inhibitor designed to overcome this resistance, is currently being tested in the New Approaches to Neuroblastoma Therapy (NANT) consortium. Aurora kinase inhibitors have been reported to disrupt MYCN, which is particularly attractive considering the lack of direct inhibitors targeting this driver in neuroblastoma. Sorafenib, a RAF kinase inhibitor, and newer PI3K inhibitors are being tested in children with neuroblastoma in an attempt to block the RAS pathway. Despite various therapies including chemotherapy, radiotherapy, immunotherapy and autologous stem cell transplantation in different neuroblastoma risk groups, most patients undergo surgical removal of the tumoral mass. This review is aimed to summarize the updated knowledge about the neuroblastoma, pathogenesis, it's essential genetic pathways and the current available therapeutic options for neuroblastoma.