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Editorial
. 2023 Apr 14;29(8):1377-1380.
doi: 10.1158/1078-0432.CCR-22-3882.

Scratching the Surface: NECTIN-4 as a Surrogate for Enfortumab Vedotin Resistance

David H Aggen  1 , Carissa E Chu  2 , Jonathan E Rosenberg  1
Affiliations
Editorial

Scratching the Surface: NECTIN-4 as a Surrogate for Enfortumab Vedotin Resistance

David H Aggen et al. Clin Cancer Res. .

Abstract

Clinical data with enfortumab vedotin (EV) suggest that most bladder cancers overexpress NECTIN-4. A recent article shows that NECTIN-4 membranous expression changes with progression to metastatic disease and that low NECTIN-4 expression in metastatic biopsies is potentially associated with EV resistance. These data argue for incorporation of NECTIN-4 expression into future biomarker strategies. See related article by Klümper et al., p. 1496.

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Conflict of interest statement

COI:

D. Aggen: Consulting Fees and Trial Funding: Seattle Genetics, Astellas. Consulting Fees: BMS, 2Seventy bio. CME: MJH LifeSciences, Curio Sciences.

J. Rosenberg: Consulting Fees and Trial Funding: Bayer, Seattle Genetics, AstraZeneca, Roche/Genentech, Astellas, QED Therapeutics. Consulting Fees: BMS, Merck, Pfizer, Pharmacyclics, Boehringer Ingelheim, GSK, Infinity, Janssen, Mirati, EMD-Serono, Gilead, BioClin, Lilly, Tyra Biosciences, IMVax, Aadi, Hengrui. CME: Research to Practice, MJH LifeSciences, Medscape, UpToDate, Clinical Care Options, OncLive. Honoraria: EMD-Serono, Pfizer, MashupMedia, Astellas

Figures

Figure 1.
Figure 1.
Nectin-4 Cell Surface Expression Changes With Progression to Metastatic Disease. A) Quantification of nectin-4 expression in primary tumor samples by Klümper et al. (1) showed that 80.3% of primary tumors express detectable nectin-4. In paired metastatic biopsies, most tumors decrease nectin04 expression by H-Score (59.1%), while others increase nectin-4 expression (19.0%). Quantification of nectin-4 in metastatic biopsies by quartile is shown (Fig 1A, bottom). B) Nectin-4 expression permits binding of enfortumab vedotin and deliver of a Monomethyl auristatin E (MMAE) payload (left). Stromal cell expression of nectin-4 may permit bystander killing of nectin-4 negative tumors cells (right). (Image created with BioRender.com.)
See this image and copyright information in PMC

Comment in

Comment on

References

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