Nectin4-targeted molecular imaging in solid tumors: Current status and future perspectives

Nectin cell adhesion molecule 4 (Nectin4), a Ca²⁺-independent immunoglobulin-like cell adhesion molecule, plays a role in both physiological and pathological processes. Nectin4 is physiologically expressed at minimal levels in most normal adult tissues; however, it is significantly upregulated in various solid tumors. It can drive cell proliferation, metastasis, angiogenesis, adhesion, recurrence, and DNA mismatch repair in tumors, leading to poor prognosis. Notably, the United States Food and Drug Administration has approved enfutumab vedotin, a novel antibody-drug conjugate targeting Nectin4, for the therapy of urothelial carcinoma, highlighting the significance of Nectin4 in targeted therapy. However, accurate diagnosis and evaluation of patients is also important. Visualization of Nectin4 expression levels can be achieved with molecular imaging, including positron-emission tomography, single-photon emission computed tomography, and near-infrared fluorescence imaging. Incorporating Nectin4-targeted molecular imaging into clinical practice is vital for the diagnosis, differentiation, treatment decision, efficacy evaluation, and prognosis prediction of a broad spectrum of solid tumors. We reviewed research advances in Nectin4-targeted molecular imaging, focusing on theranostic applications in different tumor types, including breast, urothelial, gastric, pancreatic, ovarian, colorectal, and other cancers. We also evaluated the present situation by investigating research progress, diagnostic performance, and limitations. Finally, we discuss the challenges associated with clinical implementation and present our views on advancing this area to guide future research.