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The predominant and invariably lethal form of pancreatic cancer—ductal adenocarcinoma—is characterized by an enveloping fibrotic stroma of excessive connective tissue and cells that forges rock-hard tumors. These tumors are refractory to essentially all therapies; gemcitabine, the standard-of-care chemotherapeutic drug, extends survival by only a few weeks. It has long been surmised that these pathological and clinical features are interconnected. On page 1457 in this issue, Olive et al. (1) confirm this notion, showing that cancer-associated fibroblasts in pancreatic ductal adenocarcinoma are responsible for a poorly vascularized architecture that imposes a barrier to drug delivery. Removing these fibroblasts stimulated the formation of new blood vessels (angiogenesis), improved drug delivery, and extended life span in a de novo mouse model of the disease. This study defines biophysical properties endowed by the tumor microenvironment that contribute to its therapeutic intractability and raises new questions about the role of the microenvironment in the development of this uncontrollable cancer.
Comprehensive Cancer Center, Diabetes Center, and Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94143–0534, USA.
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