|dc.contributor.author||Vallath, Sabarinath S.||
|dc.identifier.citation||Vallath, S.S. 2013. Studying the role of integrin αVβ6 in pancreatic cancer. Queen Mary University of London.||en_US
|dc.description.abstract||Pancreatic cancer is often referred to as the “silent killer“ due to the asymptomatic
nature of the disease in the early stages and the extremely poor prognosis overall.
The average one-year survival rate for PDAC patients is 24% (American Cancer
Society, facts and figures, 2010), decreasing to 5%-6% over 5 years (WHO report,
Pancreatic cancer, 2010). Only 20% of patients are suitable for surgical resection at
the time of diagnosis and treatment options available to PDAC patients have not
improved significantly over the past few decades. Thus novel therapeutic approaches
are essential to treat this disease. Our experimental, clinical and pre-clinical data
suggest integrin αvβ6 may be a suitable target.
Bioinformatics studies using the Pancreatic Expression Database revealed that the
β6 gene (ITGB6) was highly up regulated in pancreatic ductal carcinoma (PDAC)
compared with normal pancreas. Further analysis carried out showed that there was
a significant correlation between ITGB6 expression at the mRNA level and survival in
a cohort of 292 PDAC patients. Immunohistochemistry analysis on two separate
patient cohorts (n=118 and n=147) showed that normal pancreas lacked αvβ6
expression whereas 91% of PDAC tissues expressed αvβ6 at the protein level.
There was no significant correlation between αvβ6 expression and survival at the
protein level in both cohorts of patients tested.
Flow cytometry and Western blotting analyses on a panel of PDAC cell lines
confirmed expression of αvβ6 in PDAC cell lines. This study investigated the
functional role of αvβ6 in PDAC cell lines. Antibody mediated function blockade of
αvβ6 significantly inhibited proliferation in a dose dependent manner, specifically in
αvβ6 positive PDAC cell lines. A significant reduction in migration and invasion was
also observed in a panel of αvβ6 positive PDAC cell lines when treated with an αvβ6
function-blocking antibody. αvβ6 targeted antibody mediated therapy in combination
with gemcitabine significantly inhibited tumour growth in a physiologically relevant
pre-clinical subcutaneous xenograft model of PDAC.
These data reaffirms that αvβ6 is a potential novel therapeutic target and an αvβ6
specific function-blocking antibody can be used as a novel agent to treat pancreatic
|dc.description.sponsorship||Pancreatic Cancer Research Fund (PCRF); Howard-Kerr scholarship; ORSAS scholarship from Queen Mary University of London.||en_US
|dc.publisher||Queen Mary University of London||en_US
|dc.title||Studying the role of integrin αVβ6 in pancreatic cancer||en_US
|dc.rights.holder||The copyright of this thesis rests with the author and no quotation from it or information derived from it may be published without the prior written consent of the author||