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Updated: Aug 21, 2026
Identification of OTX1 and OTX2 As Two Possible Molecular Markers for Sinonasal Carcinomas and Olfactory Neuroblastomas
Published on: February 28, 2019
Systemic Therapy for High-Grade Olfactory Neuroblastoma: From Molecular Lineages to Targeted and Immune Strategies
Bin He1, Lin Ling Li2, Yu Tan3
1Department of Oncology and Radiotherapy, Chengdu Qingbaijiang District People's Hospital, Chengdu, Sichuan, 610300, People's Republic of China.
Abstract:
Advanced olfactory neuroblastoma (ONB) remains a therapeutic challenge because evidence for systemic treatment is derived largely from small retrospective series and extrapolation from related neuroendocrine malignancies. This narrative review brings together diagnostic pathology, multi-omics classification, contemporary guideline-based management, and emerging systemic approaches for high-grade, recurrent, or metastatic ONB. Neural and Basal molecular programs provide a useful biological framework, but they are not validated tools for treatment selection. Delta-like ligand 3 (DLL3)-directed therapy and epigenetic-immune combinations are supported mainly by lineage-based or preclinical evidence, whereas somatostatin receptor (SSTR)-directed strategies and immune checkpoint blockade have generated only limited ONB-specific clinical data. All remain investigational. The first prospective immunotherapy trial in recurrent or metastatic ONB did not meet its objective-response endpoint, although prolonged disease stabilization was observed in a subset of patients. We therefore outline a practical approach that preserves established multidisciplinary care while using molecular and immune profiling to clarify diagnosis and guide clinical-trial referral. Routine biomarker-directed systemic therapy will require prospective multicenter validation using standardized assays and predefined biomarkers.
Insights
Advanced olfactory neuroblastoma (ONB) treatment is challenging. Emerging therapies like DLL3-directed, epigenetic-immune, and SSTR-directed strategies show promise but require further validation for high-grade ONB.
Area of Science:
- Oncology
- Neuroscience
- Genomics
Background:
- Advanced olfactory neuroblastoma (ONB) presents significant therapeutic challenges.
- Current treatment evidence relies on limited retrospective data and extrapolation from related neuroendocrine tumors.
- High-grade, recurrent, or metastatic ONB requires novel systemic treatment strategies.
Purpose of the Study:
- To review diagnostic pathology, multi-omics classification, and management of advanced ONB.
- To evaluate emerging systemic therapies, including DLL3-directed, epigenetic-immune, and SSTR-directed approaches.
- To propose a practical approach for managing advanced ONB, integrating molecular profiling and clinical trial referral.
Main Methods:
- Narrative review synthesizing data on ONB pathology, classification, and treatment.
- Analysis of molecular programs (Neural and Basal) for biological framework.
- Evaluation of evidence for investigational systemic therapies (DLL3, epigenetic-immune, SSTR, immune checkpoint blockade).
Main Results:
- Molecular programs offer a biological framework but lack validated treatment selection utility.
- DLL3-directed and epigenetic-immune therapies have preclinical/lineage-based support.
- SSTR-directed strategies and immune checkpoint blockade show limited ONB-specific clinical data; all remain investigational.
- The first prospective immunotherapy trial did not meet its primary endpoint but showed disease stabilization in some patients.
Conclusions:
- Advanced ONB systemic therapy requires further prospective validation.
- Multidisciplinary care combined with molecular profiling is crucial for diagnosis and clinical trial guidance.
- Standardized assays and predefined biomarkers are necessary for routine biomarker-directed therapy.
