GU Cancers 2025 | Emerging biomarkers of response to EV in urothelial carcinoma
Xin Gao, MD, Massachusetts General Hospital Cancer Center, Boston, MA, comments on emerging biomarkers of response to nectin-4 in urothelial carcinoma, noting that high expression of nectin-4 is observed in most tumors, and that correlation between expression levels and response to enfortumab vedotin (EV) has been observed. However, further research is needed on the mechanisms of resistance to nectin-4 targeting antibody-drug conjugates (ADCs), where it may be related to resistance to the chemotherapy payload rather than loss of target expression. This interview took place at the ASCO GU Cancers Symposium 2025 in San Francisco, CA.
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Transcript
Yeah, so I think in terms of nectin-4, expression is quite high in urothelial cancers. A vast, vast majority of tumors will express nectin-4, but we do know that, at least within enfortumab vedotin, there’s been emerging data that the level of expression, the amplification in some cases does correlate with response. So there is an effect in terms of the expression of the target in terms of treatment efficacy, treatment response...
Yeah, so I think in terms of nectin-4, expression is quite high in urothelial cancers. A vast, vast majority of tumors will express nectin-4, but we do know that, at least within enfortumab vedotin, there’s been emerging data that the level of expression, the amplification in some cases does correlate with response. So there is an effect in terms of the expression of the target in terms of treatment efficacy, treatment response. Beyond that, there’s actually relatively little known about the mechanisms of, say, resistance to nectin-4 targeting ADCs. There’s some data to suggest that it really isn’t so much about loss of target, that it’s more potentially a resistance to the actual chemotherapy payload. And so therefore, again, another rationale for developing a different nectin-4 targeting ADC.
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