Siege, Webster's definition: the act or process of surrounding and attacking a fortified place in such a way as to isolate it from help and supplies for the purpose of lessening the resistance of the defenders and thereby making capture possible.
There's not a more apt description of metastasis to be found in any textbook of medicine. A state of siege is so apropos of what the breast cancer patient faces; but reinforcements for the defense may be on their way!
BACKGROUND: Breast cancer may erupt in errant cells in the breast, quite possibly due to (in many cases) a virus. However, the real threat imposed by this malignancy does not issue from the tumor that grows in the breast, but from the terrorist colonies it seeds elsewhere in the body - that is, metastasis.
Good news: a woman from Australia heads the calvary on its way to help
Dr. Belinda Parker of Melbourne compared the genetic profile of cancer cells taken from the primary tumor, located in the breast, and cancer cells taken from metastasis seeded into the bone from those primary tumors. She wanted to compare these two groups of cancer cells to see if she could identify any genetic changes that might provide clues as to how and why those primary tumor cells were able to escape the immune system and set up shop in bone.
BACKGROUND: Scientists have known for decades that primary tumors and their metastatic offspring differ in many respects. Often, metastatic cells appear more primitive, behave more aggressively, and are typically more difficult to kill. Too, their receptors tend to change: what may have begun in the breast as slow-growing, Grade I, estrogen-positive tumors can easily morph into fast-growing, Grade III, estrogen-negative metastasis.
You see, cancer cells never stop tryng to adapt. It's their mission to live forever, stay ahead of the game, and keep well in front of the soldiers sent to fight them - surgeons, medical oncologists, radiation oncologists, and the like.
OK, back to our good woman in Australia, Dr. Parker.
So, when she examined the two sets of cancer cells, those from primary tumors and those from tumors metastatic to bone, she found one gene in particular, Irf-7, that had been eliminated from primary tumor cells compared to those metastatic to bone.
Hmmm. What does Irf-7 do?
Well, that's the gene that regulates interferon.
Oh, yeah. Remind me again, what does interferon do?
Yeah, it allows the body to recognize foreign invaders ... evil cells that want to penetrate your fortress. Actually, interferon is made by specific white blood cells in the body - think of them as your "National Guard". Typically, interferon is used to ferret out viruses. Hmmm, that's interesting if it's true that 40-70% of breast cancer is caused by a virus... but back to Parker ...
So, Parker discovered that breast cancer cells that had set up shop in bone were able to escape immune surveillance because they had eliminated Irf-7.
Then Parker tried to repair the damage.
She took the metastatic breast cancer cells that she'd isolated from the bone of women with metastatic breast cancer .... you see, she moved from her discovery in mice right to the bedside where she could do the most good .... and she inserted the missing Irf-7 gene back inside the cells.
Guess what? Once Irf-7 was put back into the metastatic cancer cells, the immune system started wiping them out again.
Parker examined metastatic breast cells taken from 800 patients: her experiments with replacing the missing Irf-7 prolonged survival and decreased the likelihood of bone metastasis.
Parker was also able to achieve similar results just by exposing the metastatic cells to interferon; thus administering Interferon is a therapeutic alternative worth testing.
Thank you, Dr. Parker.
Reference: B. Parker, 2012, Nature Medicine, "Silencing of Irf-7..."