Too often the surgical removal of cancer or its elimination through chemo or radiotherapy isn't the end of the story, but where do the relapses come from? Part of the explanation may lay in what are known as cancer stem cells, which could be thought of as little seedlings that hide away in the body's tissues until they feel the time is right to return to action. A newly discovered molecule has raised hopes of cutting these crafty critters off at the source, with early experiments demonstrating how it can latch onto cancer stem cells and starve them of what they need to survive.
Cancer stem cells were first identified in the mid-1990s by researcher John Dick, who found that they could drive certain types of cancer as a result of their ability to evade existing treatments, which instead focused on killing fast-growing cancer cells. This discovery spawned a new branch of cancer research, which today is producing some very promising advances, such as nanoparticles engineered to seek them out and destroy them.
William Taylor, a biological scientist at the University of Toledo, likens cancer stem cells to dandelions living amongst a well-kept lawn.
"You could chop the plant off, but it will drop a seed," he says. "You know the seeds are there, but they're hiding. You pull one weed out and another comes up right after it. Cancers can be like this as well."
Taylor and his colleague Viranga Tillekeratne were actually investigating ways to improve existing chemotherapy drugs when they made their discovery. More specifically, they were working to develop new and improved versions of anti-cancer agents epothilone and Taxol, and when drilling down into their molecular structures unearthed some new possibilities.
"In this process we synthesized a molecule which killed selected cancer cell lines by a mechanism different from that of epothilone and Taxol," Tillekeratne tells New Atlas. "Further simplification of structure resulted in the identification of these small molecules with the reported anticancer activity."
Based on earlier evidence, the scientists already suspected that their newly uncovered molecules could pose a threat to cancer stem cells, so they devised some experiments to put these inklings to the test. This involved engineering cells to behave like aggressive breast cancer cells and cancer stem cells, and pitting them against the new molecules in cell cultures to see how they fared.
The cancer stem cells proved very sensitive to the molecules, and the researchers say this is because the molecules appear to latch onto them and prevent them absorbing a nutrient that is key to their survival, an amino acid called cystine. This in turn causes them to die off, which the scientists believe is due to the lack of cystine resulting in shortages of glutathione, a molecule in the cell that is key to maintaining its defenses.
"Blocking cystine causes a drop in glutathione and an increase in free radicals that damage cell membranes causing cell death," Taylor tells us.
As it stands there are no drugs that can kill cancer stem cells specifically, so this newly discovered molecule is cause for cautious optimism. Given its tendency to so selectively target cancer stem cells the team imagine it could one day be administered with other chemotherapy drugs for more effective treatments. But they have also had some early success testing it with sarcoma and some breast cancer cells, so using it as a standalone cancer therapy isn't out of the question either.
"To be clear we are at a very early stage in this research, which is not to say there is no promise, just that much work is still needed to develop our molecules as cancer drugs," says Taylor.
Tillekeratne will continue testing the effectiveness of the therapy through a three-year grant from the National Cancer Institute, while this current research has been published in the journal Scientific Reports.
Source: University of Toledo
