Integrin β6 (ITGB6)

Class

Antibody-drug conjugate (camptothecin-class TOP1-inhibitor payload, glucuronide linker)

Notes

Source: https://pubmed.ncbi.nlm.nih.gov/42515977/ (PF-08046876; researched 2026-08-08)

Integrin β6 (ITGB6) is a subunit that pairs with integrin αv to form the heterodimer αvβ6, a cell-surface adhesion receptor expressed almost exclusively on epithelial cells. Under normal conditions its expression is low, but it becomes markedly upregulated in several epithelial-derived cancers and during tissue remodeling and wound repair, where it helps activate latent transforming growth factor-beta (TGF-β) and mediates cell attachment to extracellular matrix proteins. Because tumor-associated overexpression contrasts with restricted expression in healthy tissue, αvβ6 is an attractive docking site for an antibody-drug conjugate (ADC): an antibody component recognizes the receptor, is internalized by the cell, and delivers a cytotoxic payload intracellularly. In this case the payload belongs to the camptothecin class, which inhibits topoisomerase 1, an enzyme required for DNA replication, causing lethal DNA damage in dividing cells. The antibody and payload are joined by a glucuronide linker, a chemical bridge designed to remain stable in circulation and be cleaved preferentially in tumor-associated conditions, releasing the drug at the intended site. This approach broadly matters in epithelial cancers where conventional cytotoxic chemotherapy lacks selectivity, aiming to concentrate DNA-damaging activity in tumor cells while sparing normal tissue.