Abstract LBA032: Pan-cancer analysis of fibroblast activation protein alpha (FAP) expression to guide tumor selection for the peptide-targeted radionuclide therapy FAP-2286
| العنوان: | Abstract LBA032: Pan-cancer analysis of fibroblast activation protein alpha (FAP) expression to guide tumor selection for the peptide-targeted radionuclide therapy FAP-2286 |
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| المؤلفون: | Tanya T. Kwan, Minh Nguyen, Dirk Zboralski, Anne Schumann, Anne Bredenbeck, Matthias Paschke, Christian Haase, Aileen Hoehne, Ulrich Reineke, Christiane Smerling, Frank Osterkamp, Jim Xiao, Andrew D. Simmons, Thomas C. Harding, Kevin L. Lin |
| المصدر: | Molecular Cancer Therapeutics. 20:LBA032-LBA032 |
| بيانات النشر: | American Association for Cancer Research (AACR), 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Cancer Research, Oncology |
| الوصف: | Background: FAP is a membrane-bound protease with limited expression in normal tissues but high expression on cancer-associated fibroblasts abundant in the stroma of most tumors. FAP-2286 is a potent and selective FAP-targeted peptide linked to the chelator DOTA that allows for attachment of radionuclides for therapeutic and imaging applications. Assessing patterns of FAP expression in different tumor types and correlating expression with FAP-2286 uptake can help guide tumor selection for FAP-2286 therapy. Methods: FAP immunohistochemistry (IHC) was performed on FFPE tissue specimens from 16 tumor types using the SP325 antibody. Overall and tumor/stroma-specific H-scores were calculated using Visiopharm and HALO analysis, respectively. Autoradiography with 111In-FAP-2286 was performed on a subset of matched frozen tissue sections. Results: Gene expression analysis across The Cancer Genome Atlas data set revealed elevated FAP mRNA expression in multiple tumor types. A pan-tumor IHC screen confirmed that ≥30% of samples in various indications (eg, sarcoma, pancreatic adenocarcinoma, mesothelioma, head and neck squamous cell carcinoma) had high FAP expression (H-score ≥30). While in most tumor types FAP was predominantly localized to the stroma, FAP expression was also observed in tumor cells, especially in tumors of mesenchymal origin, eg, sarcoma and mesothelioma. High FAP expression was independent of tumor stage or grade and detected in both primary and metastatic samples. Multiple sarcoma and mesothelioma subtypes demonstrated high FAP H-scores, suggesting that FAP expression is not limited to a specific subtype. There was significant correlation between FAP expression observed by IHC and FAP-2286 binding as assessed by autoradiography in matched frozen tissues (Pearson r=0.73; p Citation Format: Tanya T. Kwan, Minh Nguyen, Dirk Zboralski, Anne Schumann, Anne Bredenbeck, Matthias Paschke, Christian Haase, Aileen Hoehne, Ulrich Reineke, Christiane Smerling, Frank Osterkamp, Jim Xiao, Andrew D. Simmons, Thomas C. Harding, Kevin L. Lin. Pan-cancer analysis of fibroblast activation protein alpha (FAP) expression to guide tumor selection for the peptide-targeted radionuclide therapy FAP-2286 [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr LBA032. |
| تدمد: | 1538-8514 1535-7163 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::4919ec3ab51e23af228e1117a2d26a58 https://doi.org/10.1158/1535-7163.targ-21-lba032 |
| رقم الأكسشن: | edsair.doi...........4919ec3ab51e23af228e1117a2d26a58 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15388514 15357163 |
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