Vasoactive intestinal peptide receptor 1 (VPAC1) (VPAC1)

Vasoactive intestinal peptide receptor 1 (VPAC1) is a G protein-coupled receptor that is significantly overexpressed on the surface of various common cancers, including breast, prostate, colon, and lung carcinomas, while having limited expression in most normal tissues (Reubi et al., 2000, PubMed: 10666311). This differential expression makes it an ideal target for theranostic applications, where radiolabeled VIP analogs are used for both tumor imaging and targeted therapy (Thakur et al., 2010, PubMed: 20484418). When a therapeutic radiopharmaceutical binds to VPAC1, the complex is typically internalized into the cell, allowing the radioactive payload to emit particles in close proximity to the nucleus. This radiation causes lethal damage to the cellular DNA, primarily through double-strand breaks, leading to tumor cell death. Consequently, while the DNA is the ultimate site of therapeutic action, the VIP receptor serves as the essential molecular target for specific drug delivery (Moody et al., 2016, PubMed: 26860180). Drugs targeting this system are designed to exploit the high density of VPAC1 receptors to achieve high tumor-to-background ratios, minimizing damage to healthy cells.

Other names

VIPR1Vasoactive intestinal polypeptide receptor 1VPAC1 receptorVIP receptor type 1HVPAC1PACAP receptor type II

Targeted delivery of radionuclides or cytotoxic payloads to tumor cells via high-affinity binding to surface VIP receptors, followed by receptor-mediated internalization and subsequent induction of lethal DNA damage (e.g., double-strand breaks) by the payload.