Dr Rauscher of the Wistar Institute's cancer center recently discussed some new information discovered about breast cancer metastatic cells:
"Solid tumors such as breast cancers grow their own blood supply, a process called angiogenesis. It's clear that breast tumors shed malignant cells into the bloodstream. And it's clear that most of these cells get killed by the stress of shearing off from the primary tumor, or by the immune system. But in some patients, a tiny subset of sloughed-off cells develop the colossal powers that are required to become metastatic. At what point does that happen? "That's one of the questions we still have to answer," Rauscher said.
Recently, the ability to rapidly sequence whole genomes (the entire genetic code of a cell) has enabled scientists to analyze differences between primary tumor cells and metastatic cells. Surprisingly, Rauscher said, "there is not much genetic difference."
That finding has big implications. First, metastatic cells may not have a distinctive mutation that can be used as a neat molecular target for new drugs. Second, the important difference between primary tumor cells and metastatic cells may involve which genes are turned on and off by biochemical processes. These outside-the-gene activation processes are called "epigenetic."
Depending on the organ the metastatic cells travel to, varying genes may be activated because each organ has a different "microenvironment," controlled by distinctive cellular signals. That brings up another question: Why do certain types of metastatic cells gravitate to certain organs? Metastatic breast cells, for example, often colonize the bones first, then other vital organs. So far, Rauscher said, the explanations are unclear.
When these incredibly versatile marauders arrive at a new organ, they have the characteristics of all-powerful stem cells. That means they can go dormant for long periods, then suddenly start multiplying uncontrollably. While dormant, metastatic cells are basically invisible to the immune system, as well as impervious to chemotherapy, which works by disrupting the DNA of fast-multiplying cells.
A significant recent discovery is that metastatic cells don't travel and resettle individually. Rather, they detach from a tumor and move in clusters, the better to invade and take over a new microenvironment. It's sort of like moving a whole house, rather than just the furniture, Rauscher said.
While metastatic cells may not have a neat genetic Achilles' heel, researchers areuncovering vulnerabilities. "One therapeutic approach is to find the signals that turn dormant cells on, then block those signals," Rauscher said. "In mice, we've done this.""
So there is work in progress. If its up to the mouse stage, it is progress. But it still has a long way to go. Unfortunately.