Researchers Stress Cancer Cells for Better Treatment Options

Employing metabolic stress to destroy cancer cells could create new approaches for better targeted therapies that will not hurt normal cells and have no unpleasant side effects.

Researchers from the University of Adelaide in South Australia (Adelaide) revealed that chromosomal instability, which is a major characteristic of quickly dividing cancer cells, makes them stressed and susceptible to mild metabolic disruption.

Metabolism is the normal process by which the body converts food into energy. “A common problem in treating cancers is that they don’t respond to chemotherapy, or they respond for a while, but then come back,” stated lead author Dr. Stephen Gregory, senior postdoctoral fellow with the University’s School of Molecular and Biomedical Sciences.

“One reason this happens is because a tumor is usually not made up of identical cells but rather a diverse population of cells that changes all the time, losing, and gaining chromosomes as they divide—so-called chromosomal instability. Sooner or later they change enough to be able to resist chemotherapy drugs. Our research has shown that chromosomal instability has some consequences for cells—they get stressed, and it only takes a small metabolic push to kill them.”

Traditional chemotherapy is also very toxic to all dividing cells, especially affecting cells in hair follicles, blood, and the gut lining, frequently causing hair loss, pain, and making patients unwell. “We need to find ways to target cancer cells without affecting other normal dividing cells,” said Dr. Gregory.

The researchers stimulated chromosomal instability in the fly Drosophila and discovered that the unstable cells were “on the edge” of how much stress they could endure. “This is significant because a change in metabolism is something people cope with very well normally,” said Dr. Gregory. “That means that we hope to be able to develop treatments that have no side effects on patients, but are able to kill off the unstable tumor cells that cause relapses.”

Dr. Gregory noted that this may give some support to hypotheses of alternative treatments such as going on a drastic diet. “People who have advanced cancer which isn’t responding to chemotherapy often try a range of different treatments such as a radical diet in the hope it may help,” he said. “In some situations, it may in fact work; but we hope to be able to point the way to a more targeted approach—finding the most appropriate steps for intervention in the metabolic process that will give the best results.”

The research was published October 27, 2014, in the journal Oncogene.

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University of Adelaide in South Australia