Hematology and Oncology, Inside Pediatrics

Xenograft Program Discovering New Therapies For Pediatric Cancer

Elizabeth Beierle, M.D., center, and Jamie Aye, M.D., right, run one of the few pediatric xenograft programs in the U.S. out of Children’s of Alabama.

Although the story of pediatric cancer over the past 20 years is one of success, there are still areas where the news remains grim, particularly for pediatric solid tumors. In addition, the therapies used to treat pediatric cancers can have long-lasting consequences and even increase the risk of other cancers.

Which makes identifying novel agents with better outcomes and fewer side effects so critical. Enter the xenograft approach, in which cancer tissue taken from the child is implanted into an animal model, allowing for more precise targeting of potential therapies.

“There are xenograft models in the adult population to find novel agents, but the pediatric model is very rare,” said Elizabeth A. Beierle, M.D., a pediatric surgeon at Children’s of Alabama who focuses on pediatric surgical oncology. She, along with pediatric hematologist-oncologist Jamie M. Aye, M.D., run one of the few pediatric xenograft programs in the country out of Children’s.

“These patient-derived xenografts more closely mimic what’s going on in the human,” said Beierle. Otherwise, researchers have to use cells from tumors gathered more than 50 years ago and cultured under artificial conditions. “A lot of those tumors lost the genetic and phenotypic characteristics from the original tumor,” she said. “So when we try to investigate new drugs, we often see that what happens in the tissue culture is not what’s happening in humans.”

Plus, testing compounds in a petri dish misses the reality of a cancer in a living model, including the cells that surround the tumor and the blood vessels.

The xenograft process takes time: six months to a year before the tumors grow and experiments can begin. But seven years after the Children’s initiative began, several therapies are showing promise, with some ready to move into Phase 1 clinical trials.

One is a viral therapy for pediatric solid tumors that infects tumor cells and releases an inflammatory cytokine that attracts other inflammatory cells to attack the tumor cells. Another inhibits a protein found in pediatric liver tumors.

The barrier to clinical trials, said Beierle, is funding. While the program has received strong support from community organizations, more is needed.

One thing that isn’t a problem is obtaining the biopsy tissue for the xenograft bank. “We’ve never had a family say no,” said Aye. “They understand that the research may not affect their child, but they hope it will help other children.”

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