Published July 31, 2013
It is the great paradox of cancer treatment: High doses of chemotherapy can effectively kill cancer cells, but too much radiation can ultimately kill the patient before the tumor.
However, a new study claims to have found a way to keep patients healthy and alive while administering high doses of chemotherapy – a finding that could revolutionize cancer treatments.
The key to this “cancer cure?” The intestines.
In a paper published in the journal Nature, scientists from the University of Michigan School of Dentistry detail the significance of a healthy gastrointestinal (GI) tract for patients undergoing chemo and radiation therapy. They explained that if the GI tract remains healthy and functions, a cancer patient’s chances of survival could increase exponentially.
According to lead author Jian-Guo Geng, an associate professor in the department of biologic and materials sciences at the University of Michigan, the two systems in the body most impacted by chemotherapy are the GI epithelial cells in the intestines and the bone marrow in the skeletal system. These two systems are constantly regenerating and repairing themselves at a faster rate than other biological systems, making them much more vulnerable to the toxic effects of chemotherapy and radiation. This explains why major side effects of chemo include diarrhea, constipation, nausea and vomiting, as well as various blood disorders.
“What we found is a way to stimulate intestinal stem cells,” Geng told FoxNews.com. “(The stem cells) can repair tissue damage caused by chemo radiotherapy, so those patients will tolerate chemotherapy much better. It gives enough room for clinicians to use a high dose of chemotherapy to kill cancer – and the patient can survive.”
Through a series of in vitro experiments, Geng and his team analyzed cells in the GI tract, stumbling upon an important molecule called ROBO1. They found that ROBO1 was specifically expressed in intestinal stem cells – but not in any other cells in the body. Upon this discovery, the researchers added to the cells a protein called SLIT2, which binds to ROBO1.
The result: stem cell regeneration.
“Basically, you add SLIT2, you have more intestinal stem cells,” Geng explained. “If you have more intestinal stem cells, you repair more tissue damage, just like in general cell replication. So the ability to repair damage is higher – it’s just the logical explanation.”
The researchers theorized that by increasing stem cells in the gut, the intestine and GI tract are better protected from the effects of chemotherapy, allowing cancer patients to ingest nutrients and perform critical functions without releasing intestinal toxins into the blood circulation.
To test this idea, Geng experimented with hundreds of mice with late-stage, metastatic cancer. All of the mice received a lethal dose of chemotherapy, but only half were given SLIT2 or an analogous protein called R-SPONDIN1 to stimulate intestinal cell regeneration.
Of the mice that didn’t receive the proteins, 100 percent died within two weeks of radiation treatment. But of the mice who did receive the proteins, 50 to 75 percent survived the lethal chemotherapy dose, and subsequently, the cancer. Even more encouragingly, the increase of SLIT2 and R-SPONDIN1 in the body showed no toxic side effects and did not seem to have an effect on tumor size or sensitivity.
While Geng hopes to increase patient survival to 100 percent, he is eager to move his experiment on to clinical trials, arguing that this treatment could serve as a last resort for many metastatic cancer patients.
“We’re talking about later stage metastasis,” Geng said. “If it’s early stage, you simply do surgery to remove it. But later stage metastasis, that’s the clinical challenge. With patients more tolerable to chemotherapy, you can use more chemo more frequently… Currently they don’t give a patient a very high dosage; it’s a low dosage constantly, day after day. What we find is if you give a very high dosage, treatment is a lot more effective.”
Not only could adding this protein potentially help patients survive higher doses of chemotherapy, but it may also help mitigate the toxic side effects of radiation, making patients less sick and much more comfortable throughout their cancer treatments. With so many promising implications, Geng hopes his findings will mark a turning point in the fight against cancer.
“Under the current therapeutic dose, patients cannot keep chemotherapy going,” Geng said. “But if they can better tolerate chemotherapy, then their cancer can be cured.”