Keeping Cancer from Growing by Sabotaging Its Infrastructure
Imagine trying raise a barn without getting the framework ready first: It would be a disaster. Without infrastructure, you couldn't build much of a barn – or a road, or anything else, for that matter. The same holds true for prostate cancer. Without an infrastructure in place, a cancer can't do much growing. Prostate cancer that can't spread: wouldn't that be wonderful?
Oncologist Hans-Joerg Hammers, M.D., Ph.D., the Peter Jay Sharp Foundation Scholar, is hoping that by blocking a new target – a particular fragment of collagen that is critical in helping cancer grow – he can achieve success that has so far eluded other scientists seeking to stop prostate cancer from spreading to distant sites.
"Prostate cancer cells don't grow in isolation," he explains. "In fact, for them to expand in size and to spread to the bones, they have to coax normal cells into helping them." Cancer cells, it seems, are good at drumming up recruits – getting their neighbors to help raise the barn. "Prostate cancers make surrounding cells produce new matrices and scaffold protein." This structural support not only helps the cancer cells grow, but "appears to be critical to the formation of new blood vessels to feed them." These neighborly volunteers – normal cells called fibroblasts – together with their newly formed matrix are known as stroma.
"The activation of stroma is intimately linked to prostate cancer," says Hammers, "particularly with more aggressive disease. It is also a hallmark for the abnormal bone changes that happen in men with metastatic prostate cancer." Previously, scientists hoped to stop cancer from paving the road ahead with new blood vessels – a process called angiogenesis – by targeting a pathway that involves these blood vessels. Unfortunately, this pathway, called "vascular endothelial growth factor, or VEGF," has not panned out as a way to stop metastasis.
"The VEGF pathway has failed now in several large Phase III clinical trials," notes Hammers. He believes that the stroma may make a more vulnerable and accessible target. Exciting findings by Hammers' laboratory have shown that before new cancer blood vessels can be made, other things have to be made first: The cancer cell must construct new matrix, or scaffolding; also, a certain bit of collagen has proven to be critical for the formation of blood vessels to supply new growth.
With funding from the Patrick C. Walsh Prostate Cancer Research Fund, Hammers is working to develop new agents that will block this part of the construction. Although the target is small, if it proves as important as Hammers hopes, the result might be for the cancer cell like a carpenter trying to connect boards without nails – a nonstarter.