Nectin-4: A promising prognostic marker and therapeutic target in cancer

Nectin cell adhesion protein 4 (Nectin-4), a calcium-independent immunoglobulin-like protein, has garnered significant attention in oncology due to its pronounced overexpression in malignant tumors and absence in healthy adult tissues. Elevated levels of Nectin-4 have been implicated in the pathogenesis of various cancers, including lung, breast, and urothelial carcinomas. Notably, Nectin-4 has emerged as a promising serological marker for these malignancies, facilitating early diagnosis and monitoring of disease progression. The clinical relevance of Nectin-4 is underscored by the Food and Drug Administration's approval of enfortumab vedotin (EV), the first antibody-drug conjugate targeting this protein, for the treatment of urothelial carcinoma. Ongoing clinical trials are expanding the therapeutic applications of EV, highlighting the critical role of Nectin-4 in targeted cancer therapy. Furthermore, novel therapeutic agents targeting Nectin-4 are under investigation, offering potential new avenues for cancer treatment. Despite these advancements, the precise molecular mechanisms by which Nectin-4 influences carcinogenesis and tumor progression remain inadequately understood. Challenges such as therapy-related adverse effects and the development of drug resistance further complicate the clinical management of Nectin-4-associated cancers. This review investigates the molecular functions of Nectin-4, emphasizing its diagnostic and prognostic value in cancer. We also explore the landscape of novel drug discoveries targeting Nectin-4 and provide an overview of current clinical trials aimed at utilizing this marker for therapeutic interventions. By elucidating the multifaceted role of Nectin-4 in malignancies, this article aims to advance our understanding and improve the clinical outcomes for patients with Nectin-4 overexpressing tumors.

Open Access funding provided by the Qatar National Library. SK wrote original draft, prepared all ilustrations of the manuscript; KSP helped in writing & Editing, prepared illustration as well as helped in writing; UH, ZM & QF helped in writing, prepared table, helped in editing and revieweing; MM, OMK & AAB critical reading, editing and revieweing; SU Original idea, made substantial contributions to manuscript modifications and supervision. All authors read and approved the final manuscript for publication.

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