Assessment of targets of antibody drug conjugates in SCLC
Abstract Antibody-drug conjugate (ADC) therapy has transformed treatment for several solid tumors, including small cell lung cancer (SCLC). However, significant challenges remain, including systemic toxicity, acquired resistance, and the lack of reliable biomarkers for patient selection. To enhance...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | npj Precision Oncology |
| Online Access: | https://doi.org/10.1038/s41698-024-00784-7 |
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| author | Abhishek Ajay Han Wang Ali Rezvani Omid Savari Brandon J. Grubb Karen S. McColl Suzy Yoon Peronne L. Joseph Shelby R. Kopp Adam M. Kresak Craig D. Peacock Gary M. Wildey Minh Lam Masaru Miyagi Hung-Ying Kao Afshin Dowlati |
| author_facet | Abhishek Ajay Han Wang Ali Rezvani Omid Savari Brandon J. Grubb Karen S. McColl Suzy Yoon Peronne L. Joseph Shelby R. Kopp Adam M. Kresak Craig D. Peacock Gary M. Wildey Minh Lam Masaru Miyagi Hung-Ying Kao Afshin Dowlati |
| author_sort | Abhishek Ajay |
| collection | DOAJ |
| description | Abstract Antibody-drug conjugate (ADC) therapy has transformed treatment for several solid tumors, including small cell lung cancer (SCLC). However, significant challenges remain, including systemic toxicity, acquired resistance, and the lack of reliable biomarkers for patient selection. To enhance the effectiveness of ADC therapies in SCLC, we focused on target selection in this study by investigating the expression of ADC targets - SEZ6, DLL3, CD276, and TACSTD2 - in cell lines and patient samples. SEZ6 expression was significantly elevated in various SCLC transcriptional subtypes, particularly ASCL1, and exhibited gender-specific differences, being lower in women. DLL3 was primarily observed in the ASCL1 subtype, while CD276 showed high expression in non-neuroendocrine subtypes. TACSTD2 levels were generally low and attenuated in lymph nodes and brain metastases compared to primary tumors. Our findings underscore the importance of understanding target expression patterns to optimize ADC therapy and advance precision medicine in SCLC treatment. |
| format | Article |
| id | doaj-art-d5d524aa1cf44eb68472d5f4f99153f7 |
| institution | Kabale University |
| issn | 2397-768X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Precision Oncology |
| spelling | doaj-art-d5d524aa1cf44eb68472d5f4f99153f72025-01-05T12:07:22ZengNature Portfolionpj Precision Oncology2397-768X2025-01-01911810.1038/s41698-024-00784-7Assessment of targets of antibody drug conjugates in SCLCAbhishek Ajay0Han Wang1Ali Rezvani2Omid Savari3Brandon J. Grubb4Karen S. McColl5Suzy Yoon6Peronne L. Joseph7Shelby R. Kopp8Adam M. Kresak9Craig D. Peacock10Gary M. Wildey11Minh Lam12Masaru Miyagi13Hung-Ying Kao14Afshin Dowlati15Division of Hematology and Oncology, University Hospitals Seidman Cancer Center, and Case Western Reserve UniversityDepartment of Biochemistry, Case Western Reserve UniversityDepartment of Medicine, Institute for Transformative Molecular Medicine, Case Western Reserve UniversityDepartment of Pathology, University Hospitals Cleveland Medical Center, and Case Western Reserve UniversityDivision of Hematology and Oncology, University Hospitals Seidman Cancer Center, and Case Western Reserve UniversityDivision of Hematology and Oncology, University Hospitals Seidman Cancer Center, and Case Western Reserve UniversityDivision of Hematology and Oncology, University Hospitals Seidman Cancer Center, and Case Western Reserve UniversityDivision of Hematology and Oncology, University Hospitals Seidman Cancer Center, and Case Western Reserve UniversityDivision of Hematology and Oncology, University Hospitals Seidman Cancer Center, and Case Western Reserve UniversityDepartment of Pathology, University Hospitals Cleveland Medical Center, and Case Western Reserve UniversityDivision of Hematology and Oncology, University Hospitals Seidman Cancer Center, and Case Western Reserve UniversityDivision of Hematology and Oncology, University Hospitals Seidman Cancer Center, and Case Western Reserve UniversityDivision of Hematology and Oncology, University Hospitals Seidman Cancer Center, and Case Western Reserve UniversityDepartment of Pharmacology, Case Western Reserve UniversityDepartment of Biochemistry, Case Western Reserve UniversityDivision of Hematology and Oncology, University Hospitals Seidman Cancer Center, and Case Western Reserve UniversityAbstract Antibody-drug conjugate (ADC) therapy has transformed treatment for several solid tumors, including small cell lung cancer (SCLC). However, significant challenges remain, including systemic toxicity, acquired resistance, and the lack of reliable biomarkers for patient selection. To enhance the effectiveness of ADC therapies in SCLC, we focused on target selection in this study by investigating the expression of ADC targets - SEZ6, DLL3, CD276, and TACSTD2 - in cell lines and patient samples. SEZ6 expression was significantly elevated in various SCLC transcriptional subtypes, particularly ASCL1, and exhibited gender-specific differences, being lower in women. DLL3 was primarily observed in the ASCL1 subtype, while CD276 showed high expression in non-neuroendocrine subtypes. TACSTD2 levels were generally low and attenuated in lymph nodes and brain metastases compared to primary tumors. Our findings underscore the importance of understanding target expression patterns to optimize ADC therapy and advance precision medicine in SCLC treatment.https://doi.org/10.1038/s41698-024-00784-7 |
| spellingShingle | Abhishek Ajay Han Wang Ali Rezvani Omid Savari Brandon J. Grubb Karen S. McColl Suzy Yoon Peronne L. Joseph Shelby R. Kopp Adam M. Kresak Craig D. Peacock Gary M. Wildey Minh Lam Masaru Miyagi Hung-Ying Kao Afshin Dowlati Assessment of targets of antibody drug conjugates in SCLC npj Precision Oncology |
| title | Assessment of targets of antibody drug conjugates in SCLC |
| title_full | Assessment of targets of antibody drug conjugates in SCLC |
| title_fullStr | Assessment of targets of antibody drug conjugates in SCLC |
| title_full_unstemmed | Assessment of targets of antibody drug conjugates in SCLC |
| title_short | Assessment of targets of antibody drug conjugates in SCLC |
| title_sort | assessment of targets of antibody drug conjugates in sclc |
| url | https://doi.org/10.1038/s41698-024-00784-7 |
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