Pediatrics

New Therapy Shrinks Five Types of Pediatric Cancers in Mice

Cancerous pediatric brain tumors are some of the most aggressive cancers to affect children, and are frequently fatal. They’re difficult to treat due to their proximity to sensitive brain tissue in tiny brains, and children’s bodies can rarely tolerate the side effects of the levels of chemotherapy and radiation necessary to shrink tumors.

But recently, researchers at Stanford Medicine, the Lucile Packard Children’s Hospital, and several other institutions successfully tested a promising immunotherapy treatment that shrank multiple tumor types in mouse models. Immunotherapy treatments harness the body’s own immune system to fight the cancer, and usually come with few to no side effects compared to chemotherapy drugs and radiation.

The collaborative study, published in Science Translational Medicine, showed results on the five most common types of pediatric tumors: Group 3 medulloblastomas (MB), atypical teratoid rhabdoid tumors (ATRT), primitive neuroectodermal tumors (PNET), pediatric glioblastoma (PG), and diffuse intrinsic pontine glioma (DIPG).

The Stanford researchers designed their study after the recent discovery of a molecule known as CD47, a protein expressed on the surface of all cells. CD47 sends a “don’t eat me” signal to the immune system’s macrophages—white blood cells whose job it is to destroy abnormal cells. “Think of the macrophages as the Pac-Man of the immune system,” Samuel Cheshier, lead study author and assistant professor of neurosurgery at Stanford Medicine, tells mental_floss.

Cancer cells have adapted to express high amounts of CD47, essentially fooling the immune system into not destroying their cells, which allows tumors to flourish. Cheshier and his team theorized that if they could block the CD47 signals on cancer cells, the macrophages would identify the cells on the cancerous tumors and eat them—without any toxicity to healthy cells. To do so, they used an antibody known as anti-CD47, which, as its name implies, blocks CD47 on the cancer from binding to a receptor on the macrophage called SIRP-alpha.

“It is this binding that tells the macrophage, ‘Don’t eat the tumor,’” he says. The anti-CD47 fits perfectly into the binding pocket where CD47 and SIRP-alpha interact, “like a jigsaw puzzle,” helping the macrophage correctly identify the tumor as something to be removed. “Anti-CD47 is the big power pill in Pac-Man that makes him able to eat the ghosts,” says Cheshier.

Even better, not only does…

Genetic risk of getting second cancer tallied for pediatric survivors

childhood cancer
RISK ROUNDUP Some pediatric cancer survivors carry genetic mutations that increase the risk of a later, second cancer.

WASHINGTON — A second cancer later in life is common for childhood cancer survivors, and scientists now have a sense of the role genes play when this happens. A project that mined the genetic data of a group of survivors finds that 11.5 percent carry mutations that increase the risk of a subsequent cancer.

“We’ve always known that among survivors, a certain population will experience adverse outcomes directly related to therapy,” says epidemiologist and team member Leslie Robison of St. Jude Children’s Research Hospital in Memphis. The project sought “to find out what contribution genetics may play.” The team presented their work at the American Association of Cancer Research meeting April 3.

“This is a nice first step,” says David Malkin, a pediatric oncologist at the University of Toronto. “The results validate the thoughts of those of us who believe there is a genetic risk that increases the risk of second malignancies.”

Five-year survival rates for kids with cancer have grown to more than 80 percent. But “there are long-term consequences for having been diagnosed and treated for cancer as a child,” notes Robison. Some survivors develop a later, second cancer due to the radiation or chemotherapy that treated the first cancer (SN: 3/10/07, p. 157).

The researchers examined 3,007 survivors of pediatric cancer who routinely undergo medical evaluation at St. Jude. About a third had leukemia as children. By age 45, 29 percent of this group had developed new tumors, often in the skin, breast or thyroid.

The team cataloged…