A Baylor College of Medicine research team was one of five groups to receive a five-year grant from the National Cancer Institute, part of the National Institutes of Health, to participate in the Pediatric Preclinical Testing Consortium to address key challenges related to the development of new therapies for children with cancer.

Led by Dr. Xiao-Nan Li, associate professor of pediatrics, the Baylor research team will focus on brain cancer, the leading cause of cancer-related deaths in children. 

The consortium will address an important barrier to developing new drugs for the treatment of childhood cancers: producing reliable data from studies involving laboratory and animal models that can help to prioritize which therapeutic agents to pursue in human clinical trials. 

“One of the challenges in clinical drug development is how to effectively prioritize drug candidates to ensure clinical success in cancer patients,” said Li, who also is a member of Texas Children’s Cancer Center and Baylor’s NCI Comprehensive designated Dan L Duncan Cancer Center. “As pediatric drug candidates are much more numerous than the small number of patients, it is essential to perform comprehensive preclinical testing to identify the investigational agents that are most likely to be effective in the clinic. However, such effort has been blocked for many years due to the lack of clinically relevant and molecularly accurate model systems.”

Li is a recognized leader in pediatric brain tumor model development and in vivo drug testing. He has developed a unique surgical procedure that allows for safe and rapid implantation of human brain tumor cells into various locations (cerebrum, cerebellum and brain stem) in mouse brains. These tumor models look and act like the human tumor, allowing researchers to study the disease mechanisms and test new therapeutics.

In this project, a series of in vitro and in vivo assays will be performed to accomplish two major goals:

  • To examine therapeutic efficacy – This will be performed in genetically-appropriate models using animal survival and quantitative changes of tumor regression/progression as end points.
  • To understand mechanisms of cell killing and causes of therapy resistance.

“Our objective is to make use of our unique panel of animal models to examine therapeutic efficacy of new agents and to analyze mechanisms of action and therapy resistance in high grade glioma, medulloblastoma and ependymoma. Our hypothesis is that these patient-specific model tumors will respond to anti-cancer therapies similarly to the corresponding human primary tumors, and the effective agents identified through this system would have better chances of clinical success.” 

Li has built a collaborative team for the consortium brain tumor research program, including co-principal investigator Dr. Susan Blaney, professor of pediatrics, a leader in development therapeutics and clinical trials, and Dr. Will Parsons, associate professor of pediatrics, who will direct the genomic analysis of the mouse model tumors. Also on the team from Baylor are Drs. Robia Pautler, Pulivarthi Rao, Patricia Baxter and Jack Su, along with Dr. Adekunle Adesina of Texas Children’s Hospital.

Other institutions involved in the consortium and their research areas are:

  • Albert Einstein College of Medicine, New York, N.Y. – osteosarcoma
  • Children’s Cancer Research Institute, San Antonio – sarcoma and renal cancers
  • Children’s Hospital of Philadelphia – neuroblastoma
  • Children’s Cancer Institute, Sydney, Australia – leukemia
  • Research Triangle Institute, Durham, N.C. – coordinating center