New device could improve chemotherapy

A device engineered to deliver oxygen to cancerous cells in the lab could allow researchers to evaluate a potential cancer treatment that targets tumors often missed by regular chemotherapy. A team of researchers led by assistant professor of Chemical Engineering Neil Forbes has received $330,000 from the National Institutes of Health (NIH) to investigate the new approach, which could make chemotherapy more effective and make cancer patients less ill from its side effects.

“Our hypothesis is that hypoxia (lack of oxygen) causes death in cells,” says Forbes, a chemical engineer. “So if we deliver oxygen in differing amounts to tumor cells, we should be able to manipulate their life or death.”

To investigate how starving cells of oxygen kills them, Forbes created a device he calls a “cylindroid,” which can mimic the microenvironments around cells. Within the one millimeter, pancake-like devices are concentric layers of human colon cancer cells, each in a different environment mimicking different cell physiologies. Researchers in the laboratory can then use a microscope to view the cells as if they are peering inside the body at a real human tumor. Forbes is combining the cylindroid with an oxygen delivery microchip, invented by University of Michigan electrical engineer Michel Maharbiz. By combining these two devices, the research team can very specifically alter the entire oxygen profile throughout and within different regions of a cylindroid, and thus study the role of oxygen in cancer therapies.

The approach being engineered by Forbes and Maharbiz uses a kind of reverse psychology related to cancer therapies. They plan to target the slow-growing cancer cells that most therapy ignores, instead of the rapidly growing cancer cells that therapeutic treatments normally kill. Traditional therapies target fast-growing cancer cells so the deadly toxins will not attack most of the rest of the body, whose cells are typically slow-growing. All this explains why many patients suffer nausea and hair loss during therapy, because the cells that line the gut and hair follicles happen to be fast-growing, similar to cancer cells.

One problem with current therapy, explains Forbes, is that the human body cannot tolerate continuous chemotherapy or radiation therapy. So, in between therapeutic doses, the targeted fast-growing cancer cells might die, but the non-targeted slow-growing cancer cells survive, possibly to keep the tumor alive or, even worse, spread the cancer.

“I believe these slow-growers are the key to why some therapy fails,” says Forbes. “Slow-growing cells play a big role in the re-growth of tumors during the down time between therapeutic doses. Those are the tumors that spread.”

Forbes and his team want to use his cylindroids to test some of the chemotherapeutics now being used and make them even more efficient.

“Eventually, we would hope that by looking at a person’s biopsy we can figure out what the best schedule and dosage of therapeutics is for that individual case,” he says. “We want to augment chemotherapy to increase its effectiveness.”

March 2, 2006.