Cancer-Hunting Stem Cells May Help Deliver the Drug Effectively: Study

by Iswarya on  August 30, 2018 at 5:40 PM Cancer News
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Cancer-hunting stem cells which are developed from skin cells may help track down and deliver the drug to kill brain cancer (medulloblastoma) cells hiding after surgery. The findings of the study are published in the journal PLOS ONE.
Cancer-Hunting Stem Cells May Help Deliver the Drug Effectively: Study
Cancer-Hunting Stem Cells May Help Deliver the Drug Effectively: Study

The latest in a series of laboratory breakthroughs could lead to a more effective way to treat the most common brain cancer in children.

Previously, UNC Lineberger's Shawn Hingtgen, Ph.D., and his collaborators showed in preclinical studies they could flip skin cells into stem cells that hunt and deliver cancer-killing drugs to glioblastoma, the deadliest malignant brain tumor in adults.

In their new study, the researchers reported they could shrink tumors in laboratory models of medulloblastoma, and extend life. The study is a necessary step toward developing clinical trials that would see if the approach works for children.

Hingtgen said this approach holds promise for reducing side effects and helping more children with medulloblastoma. More than 70 percent of patients with the average-risk disease live five years on standard treatment, but not all patients respond, and treatment can cause lasting neurologic and developmental side effects.

"Children with medulloblastoma receive chemotherapy and radiation, which can be very toxic to the developing brain," said Hingtgen, who is an associate professor in the UNC Eshelman School of Pharmacy, an assistant professor in the UNC School of Medicine Department of Neurosurgery, and a member of UNC LIneberger. "If we could use this strategy to eliminate or reduce the amount of chemotherapy or radiation that patients receive, there could be quality-of-life benefits."

Hingtgen and his team showed the natural ability of the stem cells to home to tumors and began studying them as a way to deliver drugs to tumors and limit toxicity to the rest of the body. Their technology is an extension of a discovery that won researchers a Nobel Prize in 2012 and showed they could transform skin cells into stem cells.

"The cells are like a FedEx truck that will get you to a particular location, and (deliver) potent cytotoxic agents directly into the tumor," Hingtgen said. "We essentially turn your skin into something that will crawl to find invasive and infiltrative tumors."

For the study, researchers reprogrammed skin cells into stem cells, and then genetically engineered them to manufacture a substance that becomes toxic to other cells when exposed to another drug, called a "pro-drug." Inserting the drug-carrying stem cells into the brain of laboratory models after surgery decreased the size of tumors by 15 times, and extended median survival in mice by 133 percent. Using human stem cells, they prolonged the life of the mice by 123 percent.

They also developed a laboratory model of medulloblastoma to allow them to simulate the way standard care is currently delivered - surgery followed by drug therapy. Using this model, they discovered that after surgically removing a tumor, the cancer cells that remained grew faster.

"After you resect the tumor, we found it becomes aggressive," Hingtgen said. "Cancer that remained grew faster after the tumor was resected."

Scott Elton, MD, FAANS, FAAP, chief of the UNC School of Medicine Division of Pediatric Neurosurgery and co-author on the study, said there is a need for new treatments for medulloblastomas that have come back, or recurred, as well as for treatments that are less toxic overall. The ability to use a patient's own cells to target the tumor directly would be "the holy grail" of therapy, according to Elton, and he believes it could hold promise for other rare, and sometimes fatal, brain cancer types that occur in children as well.

"Medulloblastoma is cancer that happens mostly in kids, and while current therapy has changed survival pretty dramatically, it can still be pretty toxic," Elton said. "This is a great avenue of exploration, particularly for the 30 percent of children who struggle or don't make it with standard therapy. We want to nudge the needle even further."

Source: Eurekalert

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