"Because CSCs have properties similar to normal stem cells, we have to find a way to attack them while keeping the adult stem cells alive," Majumdar said. To do that, the research team inactivated a receptor that is found in increased amounts in colon cancer cells: the insulin-like growth factor receptor (IGF-1R). The colon cancer CSCs seem to need a fair amount of IGF to live, more than other cells, and they can't function without the IGF receptor.

"We found that cells that survive chemotherapy show high activation of the IGF receptor and other receptors," Majumdar said. "We thought if we could inhibit or lower the receptor, we may have a treatment strategy."

Working with human colon cancer cells, the researchers manipulated the cellular genetics using small interfering RNA (siRNA) to prevent the synthesis of IGF-1R. In this way, they reduced the number of IGF receptors by half, and reduced the number of CSCs by 35%.

Questions about toxicity remain

Interestingly, Majumdar's laboratory has also had success disabling CSCs with curcumin, a principal constituent of turmeric, a spice commonly used in Indian cuisine. His studies have found that curcumin also can lower the number of IGF-1R and can reduce CSCs further when paired with the siRNA method he outlined in the current study.

The problem with combining the above mentioned anti-CSC strategies is that they can adversely affect normal adult stem cells which, if damaged, would only cause greater harm to the organism.

In addition, it is not yet clear whether reducing the number of CSCs can reduce the recurrence rate of colon cancer. However, Majumdar's laboratory has tried out the curcumin treatment with animals, with some encouraging results.

"Whether we can do this on humans without harming normal stem cells, that's the biggest challenge," Majumdar concluded.

Source: Federation of American Societies for Experimental Biology