Neuroblastoma victims average two years old when the disease is detected, most often by a parent feeling a lump in a child's abdomen. By then, the disease has often reached an advanced stage, and advanced neuroblastoma kills more than half of the children in whom it develops, despite aggressive treatment with surgery, chemotherapy, and radiation.
In August 2008, a team at University of Texas Medical Branch at Galveston described cell-culture and animal experiments that demonstrate how shutting down a single biochemical signaling connection dramatically suppresses neuroblastoma tumor formation and slows the cancer's spread.
Their investigation centered on an intercellular signaling molecule known as gastrin-releasing peptide, or GRP, and the receptor molecule with which it docks on the cell's surface. GRP activates the production of gastrin, a hormone that among other things controls the release of gastric acid in the stomach; GRP is also produced by neuroblastoma cells and acts to accelerate their proliferation.
To target GRP, the researchers took a line of aggressive human neuroblastoma cells and added short-hairpin RNAs, tiny bits of genetic material specifically designed to keep cells from making particular proteins — in this case GRP receptor molecules. Experiments with the GRP-receptor-silenced human neuroblastoma cells revealed that they grew much less quickly than unaltered neuroblastoma cells, and showed less activity on a biochemical signaling pathway that is associated with abnormal cell proliferation.
The scientists cultured the customized cells in soft agar, a gelatin-like material that gave them no surface to which they could attach themselves. Most cells need be solidly anchored to multiply and form colonies, but neuroblastoma cells thrive in soft agar suspension
To further test what effect blocking GRP/GRP receptor binding would have on neuroblastoma in experimental animals, the researchers injected their GRP receptor-silenced neuroblastoma cells into immune-deficient mice.
Although researchers are discussing the use of short-hairpin RNA and other RNA interference techniques as potential therapies for patients with neuroblastoma and other cancers, a compound that blocks the GRP receptor has already been approved by the FDA for adult use.