Charles Institute Seminar Series 2023-24: Targeting the Integrin αvβ6 for imaging & therapy of Carcinoma with Guest Speaker Prof John Marshall
Date of Talk: Friday November 24, 2023 @12pm
Location: Charles Seminar Room / Online Via Zoom
Talk Title: Targeting the Integrin αvβ6 for imaging & therapy of Carcinoma
Speaker Details: Prof John Marshall
Professor and Centre Lead for Tumour Biology
Barts Cancer Institute, London
Short Biography: John Marshall joined the lab. of the cancer metastasis expert Ian Hart at Imperial Cancer Research Fund, London in 1984, where he began his PhD studies on the role of integrins in Melanoma. After discovering a novel integrin, αvβ1, expressed by uveal but not cutaneous melanomas, he turned his attention to carcinoma Integrins, publishing novel findings that integrin αvβ6 was a pro-invasive integrin that upregulates MMP2 and MMP9. In 2004 he moved to Barts Cancer Institute in London where he developed (the now-widely used) quantitative 3D organotypic invasion assays for study of tumour-stroma interaction to help analyse integrin behaviour. His work has shown that αvβ6 represents a major target for imaging and therapy of multiple types of carcinoma. Translating these findings to the clinic is now his primary goal, incl. via human PET imaging studies by GSK. He is co-recipient of the Pancreatic Cancer UK Grand Challenge award.
Abstract for talk: The integrin αvβ6 is expressed only by epithelial cells and then usually only when cells are undergoing tissue remodeling incl. development, chronic inflammation and cancer. One-third of all carcinomas express αvβ6 and as αvβ6 promotes cancer cell invasion, and as most tissues express little or no αvβ6, targeting this integrin could have a significant effect on survival in cancer. I will describe data that high αvβ6 correlates with poor overall survival and metastasis in both breast and pancreatic cancer. Moreover, antibody blockade of αvβ6 can significantly improve survival and reduce metastasis. In the second part of the talk, I will describe discovery of the αvβ6-specific peptide A20FMDV2 and how it became an effective tool for radio-imaging αvβ6-expressing cancers. I will also describe the effective therapy of pancreas cancers using peptide-drug conjugates.
