Review of the Targeted Therapy for Advanced/Aggressive Neuroblastoma as Adjuncts to Standard Therapy

Neuroblastoma is an aggressive paediatric malignancy originating from neural crest cells. It typically presents as an abdominal mass with associated symptoms such as fever, weight loss, and bone pain. It primarily affects children below 5 years; also, it is categorised based on clinical and genetic features. Likewise, staging systems like the International Neuroblastoma Risk Group (INRG), which guides prognosis and treatment decisions, are investigated. Managing advanced or aggressive neuroblastoma remains a significant challenge due to high-risk features like MYCN (myelocytomatosis-neuroblastoma) amplification and Anaplastic Lymphoma Kinase (ALK) mutations despite advancements in treatment. Standard therapies, including surgery, chemotherapy, radiotherapy, and in some instances, immunotherapy, are available. Yet, these therapies often fail to provide a long-term cure for high-risk patients, necessitating new therapeutic approaches. Still, emerging targeted therapies offer promising adjuncts to standard treatments, focusing on molecular targets to improve outcomes. Thus, this review explores the pathophysiology of neuroblastoma, highlighting critical therapeutic targets, such as MYCN, ALK, the Paired-like Homeobox 2B gene (PHOX2B), and epigenetic alterations that drive tumorigenesis. Understanding these molecular mechanisms provides the foundation for developing targeted treatments, including ALK inhibitors, MYCN-targeted therapies, and strategies to modulate rat sarcoma (Ras) Mitogen-Activated Protein Kinase (MAPK), cell cycle regulators, and apoptotic pathways. Immunotherapies, such as monoclonal antibodies and immune checkpoint inhibitors, also show potential in combination with conventional therapies.