Pancreatic ductal adenocarcinomas (PDAs) are notoriously aggressive and resistant to treatment. They distinguish themselves further by their robust fibroinflammatory, or desmoplastic, stromal reaction and degree of hypovascularity. Recent findings have revealed multiple mechanisms of stromal complicity in disease pathogenesis and resistance. In this review, we focus on altered physicomechanics as one mechanism of what we term as 'stromal resistance' in PDA. Extremely high interstitial fluid pressures and a dense extracellular matrix combine to limit the delivery and distribution of therapeutic agents. We discuss the genesis and consequences of altered fluid dynamics in PDA and strategies to restore them.
Bibliographical noteFunding Information:
We thank members of the Hingorani Laboratory and Victor Barocas, David Byrd, David Corr, Gregory Frost, Michael Hochberg, Ian Tannock, Curtis Thompson, and Ray Vanderby Jr. for helpful discussions and John Potter for helpful discussions and comments on the manuscript. Work in the Hingorani Laboratory is supported by NCI grants CA129537, CA161112, CA152249 and CA159240 and support from the Giles W. and Elise G. Mead Foundation.
- Pancreatic ductal adenocarcinoma
- hyaluronic acid
- interstitial fluid pressure
- stromal resistance