Developing new therapies for pediatric cancers that are resistant to treatment is the focus of two research grants awarded to Baylor College of Medicine physician-scientists by Cookies for Kids' Cancer.

Dr. Jason Shohet and Dr. Jack Su both received $100,000 grants from the nonprofit organization. Both are assistant professors of pediatrics – hematology/oncology at BCM and are part of the Texas Children's Cancer Center.

"The overall cure rate for pediatric cancer is nearly 80 percent but some cancers remain hard to treat, and we still have children losing their battles against this disease," said Dr. David Poplack, professor of pediatrics at BCM and director of the Texas Children's Cancer Center. "That's why finding novel therapies is so important. These grants from Cookies from Kids' Cancer will support our researchers in their efforts to find more effective treatments for some of the most devastating types of children's cancer."

Some current treatments also have potentially severe short and long-term side effects, including deafness, cardiac and liver damage and in some cases even secondary cancers – another reason why novel therapies are so important.

Focusing on two brain tumors

The grant funding will help support Su's research on two aggressive types of brain tumors – glioblastoma multiforme (GBM) and diffuse intrinsic pontine glioma (DIPG). Pediatric patients with these types of cancers have less than a 20 percent survival rate. Su and his collaborators hypothesize that these tumors are resistant to treatment because an enzyme called poly(ADP-ribose) polymerase, or PARP, allows the tumors to effectively repair damaged DNA after chemotherapy and radiation.

Su and his research colleagues have shown that an oral PARP inhibitor, called ABT-888, improves the tumor response to temozolomide, a common chemotherapy drug, in animal models. They are currently conducting a phase I clinical trial of ABT-888 and temozolomide in children with recurrent brain tumors through the Pediatric Brain Tumor Consortium.

Su and his collaborators are also testing in animal models whether ABT-888 will make pediatric brain tumors more sensitive to radiation. If these pre-clinical experiments show that ABT-888 would augment the efficacy of radiation, they will pursue another phase I clinical trial to study the combination of ABT-888, radiation and chemotherapy in children with newly diagnosed GBM or DIPG through the consortium.

Research on neuroblastoma

Shohet, meanwhile, will use the Cookies for Kids' Cancer grant to help fund his research on neuroblastoma, a disease that accounts for almost 15 percent of pediatric cancer deaths. He will test a novel strategy using two drugs that do not damage DNA to alter two different genetic pathways that are active in neuroblastoma. One drug serves to activate the p53 pathway that has itself been shown to be effective against neuroblastoma, and the other drug blocks the P13K pathway, which is a key pathway for tumor growth and proliferation.

Key to this research is combining the activation of one pathway with the inhibition of the other, Shohet said, because they work in direct opposition to one another.

"We strongly believe that the preclinical development and testing of this approach is a promising path to reducing treatment toxicity and improving survival for children battling this aggressive cancer," Shohet said.

Cookies for Kids' Cancer is a nonprofit organization started by Gretchen and Larry Witt after their son Liam was diagnosed with neuroblastoma. Learn more about the organization at

"Our focus is on funding the most promising clinical trials that will get to children as quickly as possible," Gretchen Witt said. "We have always believed that if people learn about the need for funding, they will support the cause. These grants represent the support of thousands of people who have held bake sales, bought cookies and believed, like we do, that we can and will make a difference in the lives of children battling cancer. We are very excited about the possibilities these therapies hold and look forward to seeing them move from the lab to a treatment room as quickly as possible."

The Texas Children's Cancer Center is a joint program of Baylor College of Medicine and Texas Children's Hospital and is the pediatric cancer program of BCM's NCI-designated Dan L Duncan Cancer Center.