Researchers offer hope for children with aggressive cancer
By Jeff Carlton
The consequences of successfully treating 5-year-old Sydney Mayrell’s aggressive soft-tissue cancer were severe: Chemotherapy made her hair fall out, surgery left her facing months of physical therapy, and radiation treatment eventually could cause secondary cancers.
That’s why Dr. Rene Galindo is hopeful the discovery by researchers in his laboratory of a mechanism that blocks the ability of cancerous rhabdomyosarcoma cells to divide and grow could lead to better treatments. Rhabdo, an aggressive childhood disease, has both a high mortality rate and, for those who survive, harsh treatments that can result in disabilities and disfigurements.
“Our goal is not only to improve mortality but to come up with therapies that are gentler and better tolerated,” said Dr. Galindo, Assistant Professor of Pathology and Molecular Biology at UT Southwestern Medical Center.
Dr. Galindo’s study, published in The Journal of Clinical Investigation, identifies the role for a gene, named TANC1, to convert otherwise normal muscle cells in fruit flies into cells that behave as aggressive rhabdo-type cells. Silencing the gene prevents otherwise healthy cells from becoming cancerous and even reverts cancerous cells to a non-cancerous state. Researchers in the Galindo lab also replicated the results in human rhabdo tumor cells.
“This suggests a completely different way of caring for rhabdo – by targeting this particular gene,” Dr. Galindo said. “If we take down TANC1 activity, it essentially rescues these cells from their neoplastic state and gets them to complete their developmental process.”
In a previous fruit fly study, the Galindo lab learned that over-expression of another gene, PAX-FOXO1, caused muscle cells to improperly fuse. The latest study revealed that PAX-FOXO1 is dependent on TANC1 in making muscle cells go awry.
“That was the most surprising factor,” said lead author Dr. Usha Avirneni, a postdoctoral researcher in the lab. “We didn’t think that just knocking down one factor would have that much effect on oncogenesis.”
Other UT Southwestern researchers involved in the study were Dr. Kathleen Galindo, postdoctoral researcher; Tiana Endicott, former lab technician; Vera Paulson, M.D./Ph.D. student; and Dr. Scott Cameron, former Assistant Professor of Pediatrics and Molecular Biology.
In many ways, the back story of Dr. Galindo’s work is illustrative of UT Southwestern’s three-part mission of education, research and patient care. Dr. Galindo was educated at UT Southwestern, earning a medical degree and doctorate, and spent several years under the tutelage of Dr. Eric Olson, Chairman of Molecular Biology.
UT Southwestern has provided Dr. Galindo’s laboratory with important financial and multidisciplinary support. Funding for his work came from both the Department of Pathology and the Harold C. Simmons Comprehensive Cancer Center.
“I have a lot of loyalty to this institution,” Dr. Galindo said.
The medical center has extensive expertise in treating rhabdomyosarcoma, which is diagnosed in about 500 to 600 children each year in the United States. Dr. Stephen Skapek, Director of Pediatric Hematology-Oncology, is a nationally recognized rhabdo expert. UT Southwestern faculty physicians see as many as 20 rhabdo patients every year at Children’s Medical Center.
One of those patients was Sydney, who was just 3 when her mother felt a hard lump growing in her daughter’s left thigh. After some testing, a pediatrician told Erin Mayrell that her daughter had Stage IV rhabdo.
“I collapsed and was just bawling,” Erin Mayrell said. “I remember asking, `Why couldn’t it be me and not her?’”
After about two months of chemotherapy, Sydney’s tumor decreased from the size of an avocado to the size of a grape, becoming small enough to resect. Surgeons removed a large portion of her quadriceps muscle. After six months of physical therapy, Sydney can walk, run and skip through her home without a limp.
She also adapted well to a 54-week course of chemotherapy. Although her hair, eyelashes and eyebrows fell out, she never vomited. She quickly adjusted to the routines of hospital life, even attempting to hook up an IV to her favorite stuffed animal.
Sydney recently had her nine-month scans, and everything checked out. Now her mom is focused on the future, and the hope that rhabdo research can lead to improved treatments.
“I am so grateful for the care she received, but it would be unbelievable if no other child had to go through the severity of her treatment,” Erin Mayrell said. “Sydney is so tough. She’s everybody’s hero.”
Dr. Olson holds the Annie and Willie Nelson Professorship in Stem Cell Research, the Pogue Distinguished Chair in Research on Cardiac Birth Defects, and the Robert A. Welch Distinguished Chair in Science.
Dr. Skapek holds the Children’s Cancer Fund Distinguished Professorship in Pediatric Oncology Research.