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Updated: Feb 11, 2026
A Model for Perineural Invasion in Head and Neck Squamous Cell Carcinoma
Published on: January 5, 2017
Data-Driven prioritisation of antibody-drug conjugate targets in head and neck squamous cell carcinoma
Saskia H Hanemaaijer1, Stephanie E van Gijn2, Sjoukje F Oosting2
1University of Groningen, University Medical Center Groningen, Department of Otorhinolaryngology/Head and Neck surgery, Groningen, The Netherlands.
Background:
For patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) palliative treatment options that improve overall survival are limited. The prognosis in this group remains poor and there is an unmet need for new therapeutic options. An emerging class of therapeutics, targeting tumor-specific antigens, are antibodies bound to a cytotoxic agent, known as antibody-drug conjugates (ADCs). The aim of this study was to prioritize ADC targets in HNSCC.
Methods:
With a systematic search, we identified 55 different ADC targets currently targeted by registered ADCs and ADCs under clinical evaluation. For these 55 ADC targets, protein overexpression was predicted in a dataset containing 344 HNSCC mRNA expression profiles by using a method called functional genomic mRNA profiling. The ADC target with the highest predicted overexpression was validated by performing immunohistochemistry (IHC) on an independent tissue microarray containing 414 HNSCC tumors.
Results:
The predicted top 5 overexpressed ADC targets in HNSCC were: glycoprotein nmb (GPNMB), SLIT and NTRK-like family member 6, epidermal growth factor receptor, CD74 and CD44. IHC validation showed combined cytoplasmic and membranous GPNMB protein expression in 92.0% of the cases. Strong expression was seen in 65.9% of the cases. In addition, 86.5% and 67.7% of cases showed ≥5% and >25% GPNMB positive tumor cells, respectively.
Conclusions:
This study provides a data-driven prioritization of ADCs targets that will facilitate clinicians and drug developers in deciding which ADC should be taken for further clinical evaluation in HNSCC. This might help to improve disease outcome of HNSCC patients.
Insights
This study identifies glycoprotein nmb (GPNMB) as a promising target for antibody-drug conjugates (ADCs) in head and neck squamous cell carcinoma (HNSCC). GPNMB is highly overexpressed in HNSCC, suggesting its potential for improving treatment outcomes.
Area of Science:
- Oncology
- Translational Research
- Biomarker Discovery
Background:
- Recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) has limited palliative treatment options.
- There is a critical need for novel therapeutic strategies to improve survival in HNSCC patients.
- Antibody-drug conjugates (ADCs) represent an emerging class of targeted therapies.
Purpose of the Study:
- To prioritize potential antibody-drug conjugate (ADC) targets in head and neck squamous cell carcinoma (HNSCC).
- To identify novel therapeutic targets for HNSCC using a data-driven approach.
Main Methods:
- A systematic search identified 55 ADC targets.
- Functional genomic mRNA profiling predicted protein overexpression in 344 HNSCC samples.
- Immunohistochemistry (IHC) validated the top targets in 414 HNSCC tumors.
Main Results:
- Glycoprotein non-metastatic melanoma protein B (GPNMB) was identified as a top ADC target.
- GPNMB protein was overexpressed in 92.0% of HNSCC cases.
- Strong GPNMB expression was observed in 65.9% of tumors.
Conclusions:
- This study provides a prioritized list of ADC targets for HNSCC.
- GPNMB is a highly validated target for ADC development in HNSCC.
- Facilitating clinical evaluation of ADCs may improve outcomes for HNSCC patients.
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