Targeting inflammation in pancreatic cancer: Clinical translation.
Preclinical modelling studies are beginning to aid development of therapies targeted against key regulators of pancreatic cancer progression. Pancreatic cancer is an aggressive, stromally-rich tumor, from which few people survive. Within the tumor microenvironment cellular and extracellular components exist, shielding tumor cells from immune cell clearance, and chemotherapy, enhancing progression of the disease. The cellular component of this microenvironment consists mainly of stellate cells and inflammatory cells. New findings suggest that manipulation of the cellular component of the tumor microenvironment is possible to promote immune cell killing of tumor cells. Here we explore possible immunogenic therapeutic strategies. Additionally extracellular stromal elements play a key role in protecting tumor cells from chemotherapies targeted at the pancreas. We describe the experimental findings and the pitfalls associated with translation of stromally targeted therapies to clinical trial. Finally, we discuss the key inflammatory signal transducers activated subsequent to driver mutations in oncogenic Kras in pancreatic cancer. We present the preclinical findings that have led to successful early trials of STAT3 inhibitors in pancreatic adenocarcinoma.
Colin William Steele, Nigel Balfour Jamieson, Christopher Ross Carter, Department of Pancreaticobiliary Surgery, Glasgow Royal Infirmary, Glasgow G4 0SF, United Kingdom.
Colin William
CW
Steele
Colin William Steele, Nigel Balfour Jamieson, Christopher Ross Carter, Department of Pancreaticobiliary Surgery, Glasgow Royal Infirmary, Glasgow G4 0SF, United Kingdom.
Nina Angharad
NA
Kaur Gill
Colin William Steele, Nigel Balfour Jamieson, Christopher Ross Carter, Department of Pancreaticobiliary Surgery, Glasgow Royal Infirmary, Glasgow G4 0SF, United Kingdom.
Nigel Balfour
NB
Jamieson
Colin William Steele, Nigel Balfour Jamieson, Christopher Ross Carter, Department of Pancreaticobiliary Surgery, Glasgow Royal Infirmary, Glasgow G4 0SF, United Kingdom.
Christopher Ross
CR
Carter
Inflammation; Microenvironment; Pancreatic cancer; Stroma