Predictive role of ABC transporters in the efficacy of enfortumab vedotin for urothelial carcinoma
Abstract Objective To evaluate the correlation between ATP‐binding cassette (ABC) transporter expression and therapeutic efficacy of enfortumab vedotin (EV), an antibody‐drug conjugate targeting Nectin‐4, in urothelial cancer, as only a few studies have been conducted on this topic. Patients and met...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-01-01
|
| Series: | BJUI Compass |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/bco2.488 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832576694142107648 |
|---|---|
| author | Toshiki Kijima Atsuko Takada‐Owada Hiroki Shimoda Hidetoshi Kokubun Toshitaka Uematsu Kohei Takei Hironori Betsunoh Masahiro Yashi Kazuyuki Ishida Takao Kamai |
| author_facet | Toshiki Kijima Atsuko Takada‐Owada Hiroki Shimoda Hidetoshi Kokubun Toshitaka Uematsu Kohei Takei Hironori Betsunoh Masahiro Yashi Kazuyuki Ishida Takao Kamai |
| author_sort | Toshiki Kijima |
| collection | DOAJ |
| description | Abstract Objective To evaluate the correlation between ATP‐binding cassette (ABC) transporter expression and therapeutic efficacy of enfortumab vedotin (EV), an antibody‐drug conjugate targeting Nectin‐4, in urothelial cancer, as only a few studies have been conducted on this topic. Patients and methods This retrospective study included 20 patients with metastatic urothelial carcinoma (mUC), including bladder and upper urinary tract cancers, who were treated with EV at Dokkyo Medical University Hospital between 2022 and 2024. Immunohistochemical staining was performed on formalin‐fixed, paraffin‐embedded tissue samples. Progression‐free survival (PFS) was estimated using the Kaplan–Meier method, and differences between subgroups (e.g., Nectin‐4 and ABC transporter expression) were compared using the log‐rank test. Results Immunohistochemical analysis indicated that tumours with high ABC transporter expression exhibited shorter PFS time and poorer response to EV. Furthermore, a decrease in Nectin‐4 expression and an increase in ABC transporter expression were observed as the disease progressed from non‐muscle‐invasive to muscle‐invasive and metastatic. Patients with Nectin‐4‐positive and ABC transporter‐negative tumours had the longest PFS, underscoring the prognostic significance of these biomarkers. Conclusion To our knowledge, this study is the first to show a correlation between ABC transporter expression and EV efficacy in urothelial carcinoma. Future research should focus on optimizing treatment strategies based on Nectin‐4 and ABC transporter expression to improve outcomes. |
| format | Article |
| id | doaj-art-739118624c994fc6a66a835283b465e0 |
| institution | Kabale University |
| issn | 2688-4526 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | BJUI Compass |
| spelling | doaj-art-739118624c994fc6a66a835283b465e02025-01-31T00:14:33ZengWileyBJUI Compass2688-45262025-01-0161n/an/a10.1002/bco2.488Predictive role of ABC transporters in the efficacy of enfortumab vedotin for urothelial carcinomaToshiki Kijima0Atsuko Takada‐Owada1Hiroki Shimoda2Hidetoshi Kokubun3Toshitaka Uematsu4Kohei Takei5Hironori Betsunoh6Masahiro Yashi7Kazuyuki Ishida8Takao Kamai9Department of Urology Dokkyo Medical University Tochigi JapanDepartment of Diagnostic Pathology Dokkyo Medical University Tochigi JapanDepartment of Urology Tokyo Medical and Dental University, Dokkyo Medical University Tokyo JapanDepartment of Urology Dokkyo Medical University Tochigi JapanDepartment of Urology Dokkyo Medical University Tochigi JapanDepartment of Urology Dokkyo Medical University Tochigi JapanDepartment of Urology Dokkyo Medical University Tochigi JapanDepartment of Urology Dokkyo Medical University Tochigi JapanDepartment of Diagnostic Pathology Dokkyo Medical University Tochigi JapanDepartment of Urology Dokkyo Medical University Tochigi JapanAbstract Objective To evaluate the correlation between ATP‐binding cassette (ABC) transporter expression and therapeutic efficacy of enfortumab vedotin (EV), an antibody‐drug conjugate targeting Nectin‐4, in urothelial cancer, as only a few studies have been conducted on this topic. Patients and methods This retrospective study included 20 patients with metastatic urothelial carcinoma (mUC), including bladder and upper urinary tract cancers, who were treated with EV at Dokkyo Medical University Hospital between 2022 and 2024. Immunohistochemical staining was performed on formalin‐fixed, paraffin‐embedded tissue samples. Progression‐free survival (PFS) was estimated using the Kaplan–Meier method, and differences between subgroups (e.g., Nectin‐4 and ABC transporter expression) were compared using the log‐rank test. Results Immunohistochemical analysis indicated that tumours with high ABC transporter expression exhibited shorter PFS time and poorer response to EV. Furthermore, a decrease in Nectin‐4 expression and an increase in ABC transporter expression were observed as the disease progressed from non‐muscle‐invasive to muscle‐invasive and metastatic. Patients with Nectin‐4‐positive and ABC transporter‐negative tumours had the longest PFS, underscoring the prognostic significance of these biomarkers. Conclusion To our knowledge, this study is the first to show a correlation between ABC transporter expression and EV efficacy in urothelial carcinoma. Future research should focus on optimizing treatment strategies based on Nectin‐4 and ABC transporter expression to improve outcomes.https://doi.org/10.1002/bco2.488ABC transportersdrug resistanceEnfortumab Vedotinmetastatic urothelial carcinomaNectin‐4 |
| spellingShingle | Toshiki Kijima Atsuko Takada‐Owada Hiroki Shimoda Hidetoshi Kokubun Toshitaka Uematsu Kohei Takei Hironori Betsunoh Masahiro Yashi Kazuyuki Ishida Takao Kamai Predictive role of ABC transporters in the efficacy of enfortumab vedotin for urothelial carcinoma BJUI Compass ABC transporters drug resistance Enfortumab Vedotin metastatic urothelial carcinoma Nectin‐4 |
| title | Predictive role of ABC transporters in the efficacy of enfortumab vedotin for urothelial carcinoma |
| title_full | Predictive role of ABC transporters in the efficacy of enfortumab vedotin for urothelial carcinoma |
| title_fullStr | Predictive role of ABC transporters in the efficacy of enfortumab vedotin for urothelial carcinoma |
| title_full_unstemmed | Predictive role of ABC transporters in the efficacy of enfortumab vedotin for urothelial carcinoma |
| title_short | Predictive role of ABC transporters in the efficacy of enfortumab vedotin for urothelial carcinoma |
| title_sort | predictive role of abc transporters in the efficacy of enfortumab vedotin for urothelial carcinoma |
| topic | ABC transporters drug resistance Enfortumab Vedotin metastatic urothelial carcinoma Nectin‐4 |
| url | https://doi.org/10.1002/bco2.488 |
| work_keys_str_mv | AT toshikikijima predictiveroleofabctransportersintheefficacyofenfortumabvedotinforurothelialcarcinoma AT atsukotakadaowada predictiveroleofabctransportersintheefficacyofenfortumabvedotinforurothelialcarcinoma AT hirokishimoda predictiveroleofabctransportersintheefficacyofenfortumabvedotinforurothelialcarcinoma AT hidetoshikokubun predictiveroleofabctransportersintheefficacyofenfortumabvedotinforurothelialcarcinoma AT toshitakauematsu predictiveroleofabctransportersintheefficacyofenfortumabvedotinforurothelialcarcinoma AT koheitakei predictiveroleofabctransportersintheefficacyofenfortumabvedotinforurothelialcarcinoma AT hironoribetsunoh predictiveroleofabctransportersintheefficacyofenfortumabvedotinforurothelialcarcinoma AT masahiroyashi predictiveroleofabctransportersintheefficacyofenfortumabvedotinforurothelialcarcinoma AT kazuyukiishida predictiveroleofabctransportersintheefficacyofenfortumabvedotinforurothelialcarcinoma AT takaokamai predictiveroleofabctransportersintheefficacyofenfortumabvedotinforurothelialcarcinoma |