Scientists at the University of Michigan have discovered two molecules that when injected in conjunction with chemotherapy protected mice from its side effects. Mice were then able to tolerated lethal doses. The results published online on July 31st in the journal Nature could revolutionize cancer treatment.
In particular areas of our body we can find adult (or somatic) stem cells. These are cells that can multiply and replenish cells that are dying. They cannot make all types of cells (like the pluripotent stem cells) but a subset of them. For example, the bone marrow contains hematopoietic stem cells that make all types of blood cells. Or the crypts of the small intestine, which also contain intestinal stem cells that divide continuously and replenish the intestine cells.
For patients with advanced forms of cancer, the most widely used and sometimes unavoidable treatment is chemotherapy and radiation. Chemotherapy and radiation are used to kill cells that multiply frequently; as cancer cells have this ability, they are killed most of the time. But there are normal cells in the human body, such as the adult stem cells, that also multiply, thus bring severe side effects. Cancer cells are resilient; they are strong and can survive under extreme conditions. “The current challenge in treating the later-staged metastasized cancer is that you actually kill the patient before you kill the tumor,” says Geng, associate professor in the University of Michigan, who led the study.
Scientists hypothesized that if they could boost the intestinal stem cells (ISCs), ISCs could fix the damage occurred by chemotherapy in mice with intestinal cancer. Searching for something to cause the boost, Dr. Wei-Jie Zhou and his colleagues in Geng’s team found that two molecules, namely Slit2 and Rspo1, exist in very high amounts in mouse crypts, where the ISCs are. They found that Slit2 and Rspo1 work together and activate the ISCs; therefore they are very important for the maintenance and constant regeneration of the intestine. And when scientists injected more Slit2 and Rspo2 in the mice, they saw much enlarged villi.
Indeed, when they administered a lethal dose of chemotherapy, the control mice had reduced villi and all died within two weeks, but 70% of mice injected with Slit2 and Rspo1 survived and had a very small reduction in villi size.
However, the same research group have shown a couple of years ago that too much of Slit2 can be correlated with colorectal cancer, a cancer of the colon in the large intestine. But when they tested it in mouse models of colorectal cancer, surprisingly 60% of these mice were also protected from chemotherapy.
As a result, injection of Slit2 and Rspo1 before and during the chemotherapy might be a possible way to boost the adult stem cells and protect healthy tissues from chemotherapy, while at the same time chemotherapy kills the cancer cells equally effective.
“Now you have a way to make a patient tolerate to lethal doses of chemotherapy and radiotherapy. In this way, the later-staged, metastasized cancer can be eradicated by increased doses of chemotherapy and radiation.” said Geng. “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.”
As always, all these have yet to be confirmed in humans. The first question that arises is: would this treatment also activate any cancer stem cells? There is a huge debate whether tumors contain cancer stem cells that can self-renew and initiate tumors, even though data suggest that they probably exist. The second question scientists must answer is whether cancer cells can still become resistant to chemotherapy.
Lastly, scientists should also study if this treatment is suitable for other types of cancer. Healthy adult stem cells exist in other tissues as well. So, it looks promising that such combinatorial therapy might reduce the negative aspects of chemotherapy and increase a cancer patient’s chances exponentially.