Data-Driven prioritisation of antibody-drug conjugate targets in head and neck squamous cell carcinoma

Hanemaaijer, Saskia H; Gijn, Stephanie E van; Oosting, Sjoukje F.; Plaat, Boudewijn E. C.; Moek, Kirsten L.; Schuuring, Ed; Laan, Bernard F. A. M. van der; Roodenburg, Jan; Vugt, Marcel A.T.M. van; Vegt, Bert van der; Fehrmann, Rudolf S.N.

doi:10.1016/j.oraloncology.2018.03.005

Cited by 6 publications

(3 citation statements)

References 29 publications

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“…However, this requires proper ADC targets, which should be significantly overexpressed on the tumor cell surface for antigen recognition and capable of being internalized to guide the drugs into the tumor cells. Albeit with existing ADC targets across different cancer types reported and their priorities and usage discussed, 42 there is still a huge demand for new ADC targets for human cancer therapy.…”

Section: Discussionmentioning

confidence: 99%

High‐throughput membrane‐anchored proteome screening reveals PIEZO1 as a promising antibody‐drug target for human esophageal squamous cell carcinoma

Qin

Jiang

et al. 2022

Cancer Medicine

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Background Esophageal carcinoma is one of the most fatal cancers worldwide. In China, over 90% of esophageal cancer patients are diagnosed with esophageal squamous cell carcinoma (ESCC). Currently, the survival and prognosis of ESCC patients are not satisfying because of insufficient early screening and lack of efficacious medication. Accumulating studies have suggested that antibody‐drug conjugates (ADC) represent a promising antitumor strategy. Method Here, we carried out a specific membrane proteome screening with ESCC patients' samples using a high‐throughput antibody microarray to uncover potential targets for ADC development. Candidates were validated with expression and cytotoxicity evaluation both in vitro and in vivo. Results Our data have shown that the Piezo‐Type Mechanosensitive Ion Channel Component 1 (PIEZO1) is particularly overexpressed in human ESCC tumors and can be efficiently internalized when bound with its monoclonal antibody. Furthermore, the PIEZO1 antibody combined with monomethyl auristatin E (MMAE) can specifically kill PIEZO1 high‐expressed ESCC tumor cells by inducing cell cycle arrest and apoptosis. More importantly, the Anti‐PIEZO1‐MMAE can significantly suppress tumor progression in ESCC xenograft tumor models without any obvious side effects. Conclusion Taken together, our work demonstrates that PIEZO1 is a promising target to develop ADCs for human ESCC treatment, providing a new strategy for ESCC patients' personalized therapy.

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Section: Discussionmentioning

confidence: 99%

High‐throughput membrane‐anchored proteome screening reveals PIEZO1 as a promising antibody‐drug target for human esophageal squamous cell carcinoma

Qin

Jiang

et al. 2022

Cancer Medicine

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“…Overexpression of B7-H3 and GPNMB is associated with the risk of recurrence and of shorter overall survival [27][28][29][30][31]. B7-H3 and GPNMB are overexpressed in many solid cancers, but their protein expressions are limited in normal tissues [31][32][33][34][35].…”

Section: Discussionmentioning

confidence: 99%

TROP-2, Nectin-4, GPNMB, and B7-H3 Are Potentially Therapeutic Targets for Anaplastic Thyroid Carcinoma

Toda

Sato

Saito

et al. 2022

Cancers

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Background: Anaplastic thyroid carcinoma (ATC) is a highly aggressive thyroid tumor with a poor prognosis. However, there are limited choices for ATC treatment. Recently, the effectiveness of antibody–drug conjugates has been demonstrated in various carcinomas. Whether the targets of antibody–drug conjugates are expressed in anaplastic thyroid carcinoma remains unclear. Methods: Fifty-four patients with ATC were enrolled in this study. Tissue microarrays were constructed using the archives of formalin-fixed paraffin-embedded tissue blocks. All sections were stained with the following antibody–drug conjugate targets: human epidermal growth factor receptor 2 (HER2), nectin-4, trophoblast cell surface antigen 2 (TROP-2), glycoprotein non-metastatic B (GPNMB), and B7-H3. Results: HER2 was negative in all tissues, whereas GPNMB and B7-H3 were expressed in most ATC tissues. TROP-2 and nectin-4 were expressed in 65% and 59% of ATC tissues, respectively. TROP-2 was expressed at significantly higher levels in ATC undifferentiated from papillary thyroid carcinoma than in ATC undifferentiated from follicular thyroid carcinoma and de novo ATC. In contrast, nectin-4 expression was markedly higher in patients with de novo ATC than in those with papillary and follicular thyroid carcinoma. Conclusions: TROP-2 and nectin-4 are potential therapeutic targets for ATC undifferentiated from papillary thyroid carcinoma and de novo ATC, respectively. GPNMB and B7-H3 potential for treating all types of ATC.

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“…Immunohistochemical receptor detection is the first step to identify new potential imaging targets. EGFR, glycoprotein nonmetastatic melanoma protein B (GPNMB), and vascular endothelial growth factor (VEGF) receptors are potential imaging targets, as previous studies indicated them to be (over)expressed in HNSCC 12–15 . This study aims to evaluate receptor expression of these potential NIR fluorescence imaging targets in salvage neck dissections.…”

mentioning

confidence: 99%

Glycoprotein Nonmetastatic Melanoma Protein B as Potential Imaging Marker in Posttherapeutic Metastatic Head and Neck Cancer

Schaik

Hanemaaijer

Halmos

et al. 2020

Otolaryngol.--head neck surg.

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Objective To evaluate expression of potential molecular imaging targets epidermal growth factor receptor (EGFR), glycoprotein nonmetastatic melanoma protein B (GPNMB), and vascular endothelial growth factor (VEGF) in lymph nodes (LNs) with or without head and neck squamous cell carcinoma (HNSCC) metastases after (chemo)radiation. Study Design Retrospective study comparing receptor expression in paired lymph nodes after initial treatment. Setting A tertiary referral hospital. Subjects and Methods Salvage neck dissection specimens of 40 patients treated with (chemo)radiation were selected. LNs that contained viable tumor, reactive changes after initial treatment, and normal LNs were analyzed using immunohistochemically determined H-scores and by calculating sensitivity and specificity rates and positive/negative predictive values (PPVs/NPVs). Results EGFR expression was found in 86% and GPNMB expression in 100% of the LNs with viable tumor. VEGF expression was present in all lymph node types. For EGFR, the sensitivity rate was 86%, and specificity rate was 81%. For GPNMB, these were 100% and 75%, respectively. PPV of EGFR was 61.8% and NPV was 98.2%. These were 56.4% and 100% for GPNMB, respectively. Conclusion In residual or recurrent HNSCC lymph node metastases, both EGFR and GPNMB show tumor-specific expression in immunohistochemistry, which may prove useful in future molecular imaging in salvage neck dissections. Immunohistochemically detected VEGF expression indicates that this target is not feasible for imaging purposes in salvage surgery. Therefore, GPNMB could be a new potential imaging target showing comparable results to EGFR in immunohistochemistry.

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Data-Driven prioritisation of antibody-drug conjugate targets in head and neck squamous cell carcinoma

Cited by 6 publications

References 29 publications

High‐throughput membrane‐anchored proteome screening reveals PIEZO1 as a promising antibody‐drug target for human esophageal squamous cell carcinoma

High‐throughput membrane‐anchored proteome screening reveals PIEZO1 as a promising antibody‐drug target for human esophageal squamous cell carcinoma

TROP-2, Nectin-4, GPNMB, and B7-H3 Are Potentially Therapeutic Targets for Anaplastic Thyroid Carcinoma

Glycoprotein Nonmetastatic Melanoma Protein B as Potential Imaging Marker in Posttherapeutic Metastatic Head and Neck Cancer

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