Strategies to overcome resistance to enfortumab vedotin and pembrolizumab for patients with urothelial carcinoma: harnessing present knowledge for future advances
The combination of enfortumab vedotin and pembrolizumab (EVP) has been recently approved for patients with locally advanced and metastatic urothelial carcinoma. This combination showed a higher objective response rate and superior progression-free survival and overall survival over traditional plati...
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| Language: | English |
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Open Exploration Publishing Inc.
2025-04-01
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| Series: | Exploration of Targeted Anti-tumor Therapy |
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| Online Access: | https://www.explorationpub.com/uploads/Article/A1002307/1002307.pdf |
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| author | Albert Jang Jason R. Brown |
| author_facet | Albert Jang Jason R. Brown |
| author_sort | Albert Jang |
| collection | DOAJ |
| description | The combination of enfortumab vedotin and pembrolizumab (EVP) has been recently approved for patients with locally advanced and metastatic urothelial carcinoma. This combination showed a higher objective response rate and superior progression-free survival and overall survival over traditional platinum-based chemotherapy in the frontline setting in the pivotal EV-302 trial. Despite the success, a subset of patients has primary refractory disease, and another subset will develop secondary resistance over time. Resistance to enfortumab vedotin may include the downregulation of nectin-4 expression to minimize antibody binding, upregulation of efflux pumps against the toxin, or direct resistance by the tubulin against the toxin. Resistance to pembrolizumab includes several methods to downregulate the immune system. Additionally, the type of histology of the urothelial carcinoma likely plays an important role in resisting EVP. This review summarizes these possible mechanisms of primary and secondary resistance, potential biomarkers predictive of response and resistance, and methods to overcome the resistance to EVP. |
| format | Article |
| id | doaj-art-c8317a42c54945ab81483d08c2b6efd5 |
| institution | OA Journals |
| issn | 2692-3114 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Open Exploration Publishing Inc. |
| record_format | Article |
| series | Exploration of Targeted Anti-tumor Therapy |
| spelling | doaj-art-c8317a42c54945ab81483d08c2b6efd52025-08-20T02:11:37ZengOpen Exploration Publishing Inc.Exploration of Targeted Anti-tumor Therapy2692-31142025-04-016100230710.37349/etat.2025.1002307Strategies to overcome resistance to enfortumab vedotin and pembrolizumab for patients with urothelial carcinoma: harnessing present knowledge for future advancesAlbert Jang0https://orcid.org/0000-0002-0461-6174Jason R. Brown1https://orcid.org/0000-0001-6225-7555Division of Solid Tumor Oncology, Department of Medicine, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA; Case Comprehensive Cancer Center, Cleveland, OH 44106, USADivision of Solid Tumor Oncology, Department of Medicine, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA; Case Comprehensive Cancer Center, Cleveland, OH 44106, USAThe combination of enfortumab vedotin and pembrolizumab (EVP) has been recently approved for patients with locally advanced and metastatic urothelial carcinoma. This combination showed a higher objective response rate and superior progression-free survival and overall survival over traditional platinum-based chemotherapy in the frontline setting in the pivotal EV-302 trial. Despite the success, a subset of patients has primary refractory disease, and another subset will develop secondary resistance over time. Resistance to enfortumab vedotin may include the downregulation of nectin-4 expression to minimize antibody binding, upregulation of efflux pumps against the toxin, or direct resistance by the tubulin against the toxin. Resistance to pembrolizumab includes several methods to downregulate the immune system. Additionally, the type of histology of the urothelial carcinoma likely plays an important role in resisting EVP. This review summarizes these possible mechanisms of primary and secondary resistance, potential biomarkers predictive of response and resistance, and methods to overcome the resistance to EVP.https://www.explorationpub.com/uploads/Article/A1002307/1002307.pdfprimary resistancesecondary resistanceenfortumab vedotinpembrolizumaburothelial carcinoma |
| spellingShingle | Albert Jang Jason R. Brown Strategies to overcome resistance to enfortumab vedotin and pembrolizumab for patients with urothelial carcinoma: harnessing present knowledge for future advances Exploration of Targeted Anti-tumor Therapy primary resistance secondary resistance enfortumab vedotin pembrolizumab urothelial carcinoma |
| title | Strategies to overcome resistance to enfortumab vedotin and pembrolizumab for patients with urothelial carcinoma: harnessing present knowledge for future advances |
| title_full | Strategies to overcome resistance to enfortumab vedotin and pembrolizumab for patients with urothelial carcinoma: harnessing present knowledge for future advances |
| title_fullStr | Strategies to overcome resistance to enfortumab vedotin and pembrolizumab for patients with urothelial carcinoma: harnessing present knowledge for future advances |
| title_full_unstemmed | Strategies to overcome resistance to enfortumab vedotin and pembrolizumab for patients with urothelial carcinoma: harnessing present knowledge for future advances |
| title_short | Strategies to overcome resistance to enfortumab vedotin and pembrolizumab for patients with urothelial carcinoma: harnessing present knowledge for future advances |
| title_sort | strategies to overcome resistance to enfortumab vedotin and pembrolizumab for patients with urothelial carcinoma harnessing present knowledge for future advances |
| topic | primary resistance secondary resistance enfortumab vedotin pembrolizumab urothelial carcinoma |
| url | https://www.explorationpub.com/uploads/Article/A1002307/1002307.pdf |
| work_keys_str_mv | AT albertjang strategiestoovercomeresistancetoenfortumabvedotinandpembrolizumabforpatientswithurothelialcarcinomaharnessingpresentknowledgeforfutureadvances AT jasonrbrown strategiestoovercomeresistancetoenfortumabvedotinandpembrolizumabforpatientswithurothelialcarcinomaharnessingpresentknowledgeforfutureadvances |