Peptidic and non-peptidic αvβ6 integrin-binding molecules have been used in clinic for detection and treatment of tumors
expressing αvβ6 integrin, because this protein is expressed in malignant epithelial cells of the oral cavity, pancreas, breast, ovary,
colon and stomach carcinomas but it is not expressed in healthy adult tissue except during wound healing and inflammation. This
review focuses on the landscape of αvβ6 integrin-binding molecules and their use in cancer treatment and detection, and discusses
recent designs for tumor detection, treatment, and immunotherapy. In the last ten years several reviews about the αvβ6 integrin have
been published but no one assesses the landscape of the αvβ6 integrin-binding molecules and their role in cancer detection and treatment. Firstly, this review describes the role of the αvβ6 integrin in normal tissues, how the expression of this protein is correlated with
cancer severity and its role in cancer development. Having into account the potential of αvβ6 integrin-binding molecules in detection
and treatment of specific tumors, special attention is given to several high-affinity αvβ6 integrin-binding peptides used for tumor imaging; particularly, the αvβ6-binding peptide NAVPNLRGDLQVLAQKVART [A20FMDV2], derived from the foot and mouth disease virus. This peptide labeled with either 18F, 111In or with 68Ga has been used for PET imaging of αvβ6 integrin-positive tumors.
Moreover, αvβ6 integrin-binding peptides have been used for photoacoustic and fluorescence imaging and could potentially be used
in clinical application in cancer diagnosis and intraoperative imaging of αvβ6-integrin positive tumors. Additionally, non-peptidic
αvβ6-binding molecules have been designed and used in clinic for the detection and treatment of αvβ6-expressing tumors. Anti-αvβ6
integrin antibodies are another useful tool for selective identification and treatment of αvβ6 (+) tumors. The utility of these αvβ6 integrin-binding molecules as a tool for tumor detection and treatment is discussed, considering specificity, sensitivity and serum stability. Another use of the αvβ6 integrin-binding peptides is to modify the Ad5 cell tropism for inducing oncolytic activity of αvβ6-
integrin positive tumor cells by expressing A20FMDV2 peptide within the fiber knob protein (Ad5NULL-A20). The newly designed
oncolytic Ad5NULL-A20 virotherapy is promising for local and systemic targeting of αvβ6-overexpressing cancers. Finally, new
evidence has emerged, indicating that chimeric antigen receptor (CAR) containing the αvβ6 integrin binding peptide on top of
CD28+CD3 endodomain displays a potent therapeutic activity in a diverse repertoire of solid tumor models.