[5-18]Precision Medicine for Pediatric Brain Tumors: Protocol, Progress, Problems and Potential Solutions

报告题目:Precision Medicine for Pediatric Brain Tumors: Protocol, Progress, Problems and Potential Solutions 
报 告 人:Dr. Xiao-Nan Li(贝勒医学院儿科终身教授,德州儿童医院德州儿童癌症研究中心,神经肿瘤临床前研究项目主任) 

Professor (Tenured), Department of Pediatrics 
Director, Preclinical Neurooncology Research Program 
Texas children's cancer center 
Texas children's hospital 
Baylor College of Medicine

About Xiao-Nan Li, MD, Ph.D 
Dr. Xiao-Nan Li is a member of the Brain Tumor Program at Texas Children’s Cancer Center. 

His research interests are in the fields of cancer stem cells and experimental therapeutics of malignant brain tumors. He is particularly interested in establishing preclinical rational of various antitumor compounds, and is working closely with other clinical investigators to quickly translate the preclinical findings into clinical trials. Dr. Li’s research is also focused on the delineation of genetic pathways that are involved in the determination of drug responsiveness of brain tumor cells through comprehensive molecular analysis. The ultimate goal of his research is to identify diagnostic markers and therapeutic targets that will eventually lead to molecular based subclassification of pediatric brain tumors and more effective therapies with low toxicity. 

Dr. Li has a specific interest in developing clinically relevant animal models for preclinical drug screening and biological studies of human malignant brain tumors. Since traditional subcutaneous xenograft models do not faithfully reproduce the biology of human brain tumors and are often associated with failure or reduced efficacy of the drug/therapy in clinical trials, Dr. Li is actively engaged in the development of primary tumor-based orthotopic xenograft models through direct injection of fresh surgical specimens of patient tumors into the anatomically matched locations in the brains of immunodeficient mice. With a tumor take rate more than 70%, Dr. Li has established more than 25 xenograft mouse models of pediatric brain tumors, including medulloblastoma, glioblastoma multiforme, ependymoma, ependymoblastoma, and atypical teratoid/rhabdoid tumor. Detailed characterization showed that these models have replicated the histopathological phenotypes, invasive/metastatic growth features and genomic profiles of the original patient tumors. More importantly, Dr. Li has demonstrated that these models can be serially subtransplanted in vivo in mouse brains and stored in liquid nitrogen for long-term preservation of their tumorigenicity. This large panel of clinically relevant and patient-specific animal models has thus provided Dr. Li and his team an unprecedented opportunity to study the biology and test new therapies of pediatric brain tumors. 

Dr. Li is also interested in cancer stem cells. Although this small population of tumor cells is shown to be the seed cells of tumor initiation and the primary causes of tumor recurrence, efforts in developing effective therapies against cancer stem cells are hindered by limited tumor tissue availabilities and lack of appropriate animal models. This is because cancer stem cells, like normal stem cells, require a special microenvironment, known as stem cell niche, for survival and maintenance of their stem cell phenotypes. It is therefore critical to investigate their biology and test novel therapies in vivo in clinically relevant animal models. Dr. Li’s laboratory was the first to demonstrate that cancer stem cells are preserved in vivo in primary tumor-based orthotropic xenograft mouse models even after serial subtransplantations in mouse brains. This finding is important, because Dr. Li and his colleagues can now test new therapies that are designed to selectively target cancer stem cells in vivo in a microenvironment that is the closest to human brain tumors. Furthermore, since these models can provide a sustainable supply of biologically accurate cancer stem cell, Dr. Li can extend the scope of his cancer stem cells studies that are aimed to understand the mechanisms of action of new therapeutic strategies and to decipher the genetic pathways that govern the key biological phenotypes of cancer stem cells, including self-renewal, cell cycle regulation and drug resistance. Dr. Li is also utilizing this unique set of in vivo models to investigate the roles of cancer stem cells in the invasion and metastasis of malignant brain tumors. 

MD, Suzhou Medical College, China 
PhD, Suzhou Medical College, China 
MS, Suzhou Medical College, China 
Fellowship, Baylor College of Medicine 

Selected Memberships 
Member, America Association for Cancer Research (AACR) 
Member, Society of Neuro-oncology 
Member, Children’s Oncology Group (COG) 
Research Interests 
Cancer stem cells 

Experimental therapeutics 
Preclinical rational of various antitumor compounds 
Delineation of genetic pathways 
Molecular based subclassification of pediatric brain tumors 
Effective therapies with low toxicity