As mentioned, stromal tissue can account for as much as 90% of the bulk in pancreatic cancer tumors. Thought in the past to have been relatively inert, it is increasingly clear that this dense tissue arising from a desmoplastic process is surprisingly dynamic. Thus, it is heartening to encounter a number of recent serious research efforts aimed in a practical way to begin to try to counteract the effects of the pancreatic cancer stromal tissue in ameliorating the effects of standard treatment modalities. We have commented on two of these previous studies HERE and HERE.
Grose and colleagues from the Centre for Tumour Biology Barts Cancer Institute at Queen Mary University of London E-published the results of their pre-clinical work on February 6, 2014 in the open journal EMBO – Molecular Medicine. They studied the fibroblast system that is active in the desmoplasic process resulting in the creation of pancreatic cancer tumor stromal tissue, with particular attention to the fibroblast growth factor (FGF) signalling cascade which appears to be active in pancreatic cancer cell survival and invasion.
FGFs and their receptors are frequently overexpressed in pancreatic cancer, as well as in a number of other tumor types. The researchers particularly looked at FGF1 and FGF2 and their receptors. The respective receptors are notated as FGFR1 and FGFR2. FGF2 over-expresion appears to be correlated with poor patient outcome in pancreatic cancer.
The authors demonstrate that blocking nuclear aspects of FGFR1 and FGFR2 appears to interrupt fibroblast proliferation, thus disrupting the pancreatic cancer “microenvironment.” The practical effect of this mechanism is that pancreatic cancer cell invasion is thwarted. The authors postulate that inhibiting the fibrogen growth factor cascade by therapeutic agents may target the pancreatic cancer stroma in a manner that interferes with the natural history of pancreatic cancer and thus could enhance patient outcomes.
This is another interesting and promising piece of the puzzle.
Dale O’Brien, MD