Lyndsey Sandow
Determining the Role of Focal Adhesion Kinase on Tumor Immunogenicity and T cell Function in Tumor and Cancer Stem Cells
Summary
Immunotherapy has proven to be an effective treatment in many drug resistant tumors; however, pancreatic ductal adenocarcinoma (PDAC) has shown little response to these therapies, making it one of the most lethal cancers. It is hypothesized that PDAC’s tumor microenvironment (TME) plays a significant role in the failure of immunotherapy. Recent studies have shown that the inhibition of focal adhesion kinase (FAK) can sensitize PDAC to checkpoint inhibitors and FAK is thought to play a role in immunosuppression and fibrosis. The exact mechanism of FAK in maintaining the TME is unknown, as is its effect on tumor immunogenicity and T cell function. Building upon these studies, this project hopes to demonstrate the mechanism of FAK and elucidate its effect on tumor immunogenicity and cytotoxic T cells to enhance PDACs response to immunotherapy. FAK has also been implicated in the regulation of cancer stem cells (CSCs); however, the role of immunotherapy in limiting growth and metastasis of CSC has yet to be studied. Accordingly, the project hopes to determine the role of FAK in the expression of immunomodulatory factors in PDAC CSCs. The objective is to understand the mechanism behind FAK inhibition in both tumor and CSC in order to improve PDACs response to immunotherapy and improve disease progression and metastasis.
The PhRMA Foundation Paul Calabresi Medical Student Fellowship has allowed me to devote a year to research immunotherapy in pancreatic cancer. Because of the PhRMA Foundation’s generous support, I have gained invaluable skills in experimental design, critical thinking and lab-based research which I am excited to use in my future as a physician-scientist.
