Two Baylor College of Medicine doctors have received support for their research from Alex's Lemonade Stand, a nonprofit group dedicated to fighting pediatric cancer.

Dr. Jason Shohet, assistant professor of pediatrics – hematology/oncology and co-chair of Texas Children's Cancer Center's Neuroblastoma Program, received a two-year, $200,000 Innovation Award from the organization for his research on reprogramming neuroblastoma cancer stem cells. Innovation Awards are given by Alex's Lemonade Stand to provide seed funding for experienced investigators with a novel and promising approach to finding causes and cures for childhood cancer.

Preventing neuroblastoma

"Our major goal is to develop novel treatments to prevent neuroblastoma relapse," Shohet said. "This will have a major impact on survival for neuroblastoma, which is currently less than 40 percent."

Neuroblastoma is the most common tumor in children and accounts for 15 percent of all pediatric cancer deaths. Most deaths result from relapsed neuroblastoma, which returns after initially responding to treatment.

Shohet and his colleagues will investigate the process that enables stem cells to shut off and turn on essential pathways involved in cancer relapse.

"This information is essential for the design of entirely new, less toxic therapeutic approaches to specifically reverse or reprogram these pathways. This should force cancer stem cells to evolve into non-malignant mature cells incapable of causing disease relapse."

Pediatric AML

Dr. Maria Monica Gramatges, assistant professor of pediatrics – hematology/oncology and a pediatric oncologist at Texas Children's Cancer Center, received a two-year, $80,000 Young Investigator grant. This funding will support her research in pediatric acute myeloid leukemia (AML), where she is studying genetic markers for risk of certain treatment related toxicities, such as prolonged periods of low white blood cell counts following chemotherapy.

Gramatges is investigating genes associated with an enzyme called telomerase, looking for variations in these genes that result in reduced telomerase activity. Telomerase maintains the length of telomeres, which form a protective cap on chromosome ends and delay cellular aging. Short telomeres and reduced telomerase activity as a result of variations in telomerase genes may be associated with a risk for developing AML and bone marrow failure, as well as a heightened sensitivity to chemotherapy.

This is a significant issue, Gramatges explained, because currently there is no screening for defects in telomerase, which not only affect risk for AML but may also affect the severity of adverse events from chemotherapy. One adverse treatment effect is prolonged recovery of white blood cells, which places patients at serious risk for severe infections and is associated with increased cancer deaths.

"The results of this research may lead to screening all children diagnosed with AML for defects in telomerase, and, in those individuals where a significant mutation is found, closer monitoring for toxicities and consideration of modified treatment regimens," Gramatges said.

Young investigator grants are designed to fill the critical need for start up funds for new researchers and physicians to pursue promising research ideas.