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Exploring the effect of PAK inhibition in a 3D Pancreatic Cancer invasion model
* 1 , 2 , 1
1  School of Cancer and Pharmaceutical Sciences, King’s College London
2  Guy’s and St Thomas’ NHS Foundation Trust, London UK, King’s College London, UK
Academic Editor: Alexander E. Kalyuzhny

Abstract:

Pancreatic Ductal Adenocarcinoma (PDAC) is an aggressive cancer, with over half of patients presenting with metastatic PDAC at diagnosis. Most patients receive conventional chemotherapy which invariably faces resistance, and a key facilitator in this is the PDAC stroma which acts as a functional mediator of disease progression through bilateral crosstalk between stromal cells and cancer cells. ‘Migrastatics’ are a new drug class which target cell migration pathway effector proteins to attenuate cancer cell invasion. Improvement in PDAC treatment strategy is well-overdue and migrastatics as adjuvant therapy is one avenue gaining traction. The p21-activated kinase (PAK) family is frequently overexpressed and/or amplified in PDAC where it regulates cytoskeletal actin contractility as well as transcription. Pre-clinical PAK inhibitors have shown reduced 3D PDAC cell invasion in vitro, yet it is unknown how the PDAC stroma would respond to a PAK inhibitor and how this could affect PDAC invasion. My PhD project investigates the stellate cells response to PAK inhibition.

Keywords: Pancreatic cancer, tumour microenvironment, cell invasion, 3D in vitro assay, p21-activated kinases

 
 
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