Nectin-4 Expression Patterns in Bladder Cancer: Implications for Targeted Therapy

What is it about?

This study investigates Nectin-4 expression in urothelial bladder cancer (UBC) across 314 patients undergoing radical cystectomy. Researchers found Nectin-4 expression in 63% of primary tumors and 87% of lymph node metastases, with higher levels in metastases. Expression varied by histological and molecular subtypes, with luminal subtypes and certain histologies (e.g., micropapillary) showing higher positivity. The findings suggest that low Nectin-4 expression might predict better responses to platinum-based chemotherapy. Overall, the study highlights the heterogeneity of Nectin-4 expression and its implications for therapies like enfortumab vedotin and platinum-based treatments.

Featured Image

Why is it important?

This research is significant because it investigates the expression patterns of Nectin-4, a target molecule for the antibody-drug conjugate enfortumab vedotin (EV), in urothelial bladder cancer (UBC). Understanding Nectin-4 expression across different histological and molecular subtypes of UBC is crucial for predicting treatment efficacy and guiding personalized therapy decisions. The study's findings contribute to a more nuanced understanding of Nectin-4 expression in UBC, challenging previous assumptions about its ubiquity in advanced cases and highlighting the potential for differential response to both EV and platinum-based chemotherapy based on Nectin-4 expression levels. Key Takeaways: 1. Heterogeneity in Expression: The study reveals significant variability in Nectin-4 expression across different histological and molecular subtypes of UBC, with higher expression in luminal subtypes and lower expression in basal and mesenchymal subtypes. 2. Treatment Implications: The research suggests that Nectin-4 expression levels may predict responsiveness to both EV and platinum-based chemotherapy, with lower Nectin-4 expression potentially indicating greater benefit from platinum-based treatments. 3. Metastatic Progression: The study found higher Nectin-4 expression in lymph node metastases compared to primary tumors, indicating a potential role for Nectin-4 in metastatic progression and highlighting its importance as a therapeutic target in advanced disease.