Researchers have found a way to preserve gut health in mice that have been given very high doses of chemoradiotherapy. They say if the same works in humans, it could be a huge step towards treatments that eradicate metastatic cancer.
Jian-Guo Geng, associate professor at the University of Michigan School of Dentistry, and colleagues, describe their promising findings in a July 31st online issue of Nature.
The researchers believe their findings could eventually lead to a cure for later-staged metastasized cancer.
“People will not die from cancer, if our prediction is true,” says Geng in a statement.
In their background information, the authors note that cancer research has quite rightly concentrated on preventing cancer, detecting it early, and finding ways to target cancer cells without harming healthy cells.
However, once cancer has advanced and spread (metastasized), then treatments tend to involve intensive chemoradiotherapy (a combination of chemotherapy and radiotherapy) which damages healthy tissue, often with fatal consequences, as Geng explains:
“All tumors from different tissues and organs can be killed by high doses of chemotherapy and radiation, but the current challenge for treating the later-staged metastasized cancer is that you actually kill the patient before you kill the tumor.”
For their investigation, the team pursued a glimmer of hope: the knowledge that if the digestive tract of patients with metastatic cancer remains healthy after intensive chemoradiotherapy, then the chances of survival are hugely improved.
“If you can keep the gut going, you can keep the patient going longer,” says Geng.
In fact, the chances of survival “increase exponentially,” he adds.
In their paper, the authors describe how they identified a biological mechanism that preserves intact the digestive tract of mice as they undergo lethal doses of chemoradiotherapy.
The mechanism is to do with stem cells in the gut.
Stem cells are the body’s natural healers: they can transform into any cell type to renegerate damaged organs or tissue. When a bit of damage occurs here or there, they naturally set about regenerating tissue.
But the huge swathes of wreckage left behind by the high doses of chemotherapy and radiation that are required to treat late-stage tumors are usually too overwhelming for the natural levels of stem cells to cope with.
The mechanism that Geng and colleagues discovered causes gut stem cell regeneration to go into overdrive and launch a massive healing campaign.
Geng says the extra stem cells protect the gut and help it ingest more nutrients, allowing the body to carry out critical processes. The extra protection also prevents bacterial toxins from entering the bloodstream.
The idea is this could give the patient just enough leverage to survive intensive chemoradiotherapy while it eradicates the tumor or tumors.
The trigger for the mechanism is when certain proteins bind with a molecule on the surface of gut stem cells.
The researchers discovered this while working with cells in test tubes. They analyzed cells from the gut, and came across a cell surface receptor called Robo1. This was only present on intestinal stem cells. No other cells in the body appear to have this receptor.
When they added a protein called Slit2 to the intestinal stem cells, it bound to Robo1 and triggered the mechanism: massive stem cell regeneration was the result.
Geng and colleagues then showed that 50-75% of mice treated with Slit2 or an analagous protein survived otherwise lethal doses of chemoradiotherapy, whereas there were no survivors among mice that did not receive the proteins. Geng says:
“Now we have found a way to protect the intestine. The next step is to aim for a 100-percent survival rate in mice who are injected with the molecules and receive lethal doses of chemotherapy and radiation.”
However, he does point out that there is still much work to be done; just because something works in mice, it does not mean it will work in humans.
Another encouraging direction for metastatic cancer treatment was revealed in 2010 by another mouse study that showed how an anti-cancer agent stopped metastasis in its tracks. The agent targets a protein that is critical to cell movement.
Written by Catharine Paddock PhD