Abstract
Olfactory neuroblastoma is a rare and histologically variable malignancy arising from the olfactory neuroepithelium. While it may present indolently in early stages, aggressive or advanced forms often involve intracranial invasion, high-grade histology, and distant metastasis, leading to poor prognosis and frequent recurrence. The traditional management of olfactory neuroblastoma relies on surgical resection combined with radiotherapy, with chemotherapy applied in recurrent or metastatic settings. However, these modalities frequently fall short in high-risk cases due to resistance, recurrence, or anatomical constraints.
This review focuses on the evolving role of targeted therapy as a precision approach to treating aggressive and advanced olfactory neuroblastoma. The aim is to summarize current evidence from translational research and early-phase clinical trials regarding therapies directed at molecular abnormalities commonly identified in these tumors. Key genetic alterations include mutations in tumour protein p53 (TP53), dicer 1 ribonuclease III (DICER1), fibroblast growth factor receptor 3 (FGFR3), isocitrate dehydrogenase 2 (IDH2), anaplastic lymphoma kinase (ALK), and aberrant activation of the phosphatidylinositol 3-kinase (PI3K)/mechanistic target of rapamycin (mTOR) pathway.
Therapeutic strategies under investigation include tyrosine kinase inhibitors (e.g., erlotinib, sorafenib), ALK inhibitors (e.g., crizotinib), mTOR inhibitors (e.g., everolimus), and immune checkpoint inhibitors (e.g., nivolumab). While early data are promising, robust clinical validation remains limited. This review also addresses the current limitations of targeted therapy in olfactory neuroblastoma, such as tumour heterogeneity, lack of large-scale trials, and challenges in molecular profiling. Continued integration of genomic data into clinical decision-making may enable more effective, individualized treatment strategies for this rare but formidable malignancy.