Research Advances from the Pancreatic Cancer Stromal Reprogramming Consortium (PSRC)

Using pancreatic tumor explant models, researchers with the Columbia University PSRC Project revealed a cascade of cellular signals that suppress angiogenesis (i.e., formation of new blood vessels) in pancreatic cancer.

Researchers with the University of Michigan PSRC project found that WT1-expressing mesenchymal cells in the normal pancreas can give rise to inflammatory cancer-associated fibroblasts (CAFs) in pancreatic tumors, which promote cancer growth independent of immune cell responses. 

Investigators with the University of North Carolina showed that CAF subtypes have an additive effect over tumor-intrinsic subtypes in predicting patient survival with or without neoadjuvant therapy in pancreatic cancer. According to the authors of the study, "Molecular subtyping of both tumor and CAF compartments of PDAC may be important steps in selecting first-line systemic therapy." 

Researchers with the University of Illinois at Urbana-Champaign PSRC Project showed that depletion of fibrinogen suppresses pancreatic tumor growth and metastasis in preclinical models by reprogramming the tumor microenvironment toward tumor-restraining, fibroblast-enriched stroma. They also found that targeting fibrinogen with an antisense oligonucleotide or nanoparticles containing small interfering RNAs (that are currently being clinically tested) may be potential therapies for pancreatic cancer.
 

Investigators with the Dana-Farber Cancer Institute PSRC Project performed an integrative, genome-scale analysis of genetic dependencies and cell surface targets in pancreatic ductal adenocarcinoma (PDAC). This work showed that CDS2 is a synthetic lethal target in cancer cells expressing signatures of epithelial-to-mesenchymal transition, identified biomarkers and co-dependencies of the KRAS oncogene, and revealed potential combination treatment strategies for targeting different pancreatic tumor phenotypes. 

Investigators  with the University of Illinois at Urbana-Champaign PSRC Project developed a new nanomaterial, specifically called DNA origami-cyanine nanocomplexes, for the precise imaging of KRAS-mutant pancreatic cancer cells in the tumor microenvironment. This new approach could potentially enable the selective targeting and elimination of pancreatic tumor cells while preserving surrounding normal tissues to, ultimately, improve treatment for a cancer that often has a very poor prognosis.