Katherine E. Warren, M.D.
Dr. Warren headed the Pediatric Neuro-Oncology Section and led preclinical and clinical efforts in developing new therapeutic strategies for the treatment of children with tumors of the central nervous system. She has extensive experience in drug development for children with CNS tumors, including preclinical pharmacokinetic studies, and early phase clinical trials in children. Her research entailed a multifaceted approach in efforts to develop clinical trials with biologic and pharmacologic rationale and included a) experimental therapeutics and noninvasive analysis of individual patients, including multiparametric imaging, b) utilization of preclinical models to study CNS pharmacology of agents and alternate delivery methods, and c) study of tumor biology to identify potentially druggable targets.
1) brain tumors, 2) pediatric clinical trials, 3) diffuse intrinsic pontine glioma (DIPG),
4) drug delivery, 5) multiparametric imaging, 6) pharmacokinetics
Pediatric Neuro-Oncology Section
Pediatric brain tumors represent a heterogeneous group of diseases. A significant proportion of tumors are considered benign or low-grade. The 5-year survival for these children is currently over 70%.
However, for those children with malignant tumors including diffuse intrinsic brainstem gliomas and high-grade gliomas and those with recurrent malignant tumors, the 5-year survival is dismal. Despite neurosurgical and radiotherapeutic advances, no significant improvement in survival has been made for patients suffering from these tumors in several decades.
The armamentarium for the treatment of pediatric central nervous system (CNS) tumors includes surgery, radiation and chemotherapy. Although surgery may be curative for focal, benign tumors, adjuvant therapy is necessary for invasive, malignant lesions. Radiation therapy is toxic to the developing brain and avoided or deferred if possible, in very young children. Although chemotherapy plays an important role, improvement in the survival of pediatric patients with malignant gliomas and recurrent malignant tumors, has been modest, at best, and for some tumors, such as diffuse intrinsic pontine gliomas, no chemotherapy has ever demonstrated an ability to improve patient outcome. Few agents are available for clinical development in children.
In addition to the sometimes disparate tolerability and pharmacokinetics between adult and pediatric patients, pediatric CNS tumors differ from adult CNS tumors in histology, biology, pathophysiology and location, and therefore efficacy data available for adults may not apply to pediatric patients. Rational drug development based on relevant pharmacokinetics (PK), such as CNS penetration, is infrequently performed, and early studies instead frequently aim to identify a maximum tolerated dose rather than a targeted effective dose.
The major goals of the Pediatric Neuro-Oncology Section are rational, PK-based, drug development in the pediatric population, and investigation of novel therapeutic approaches, such as convection-enhanced delivery. Assessing tumor characteristics and treatment effects noninvasively is particularly important in pediatric neuro-oncology given the technical and ethical limitations of repeat tissue sampling in these children. Defining and incorporating innovative endpoints in clinical trials designed to determine the biologic and therapeutic activity of new agents is a major focus of our research.
Selected Key Publications
- J Natl Cancer Inst. 93: 1401-5, 2001. [ Journal Article ]
- J. Neurosurg. 107: 190-7, 2007. [ Journal Article ]
Predicting outcome of children with diffuse intrinsic pontine gliomas using multiparametric imaging.Neuro-oncology. 13: 904-9, 2011. [ Journal Article ]
- Neuro-oncology. 14: 326-32, 2012. [ Journal Article ]
- J. Neurooncol. 113: 341-2, 2013. [ Journal Article ]
Dr. Warren received her B.S. in Medical Technology in 1982 and her M.D. from Tufts University School of Medicine in 1990. She completed a residency in pediatrics at Children's National Medical Center, followed by a fellowship in pediatric oncology at the National Cancer Institute. She is board certified in pediatrics and pediatric hematology/oncology. Dr. Warren is a Senior Investigator in the Pediatric Oncology Branch, specializing in neuro-oncology. Her research interests include performance of clinical trials, particularly in children with tumors of the central nervous system, non-invasive evaluation/imaging of the brain, and neurotoxicity resulting from tumors and their treatment.
|Rafael Cruz Garcia||Biologist (Contr.)|
|Cindy Lester McCully B.S.||Biologist|
|Priya Shankarappa||Postbaccalaureate Fellow (CRTA)|
|Kim Walker R.N.||Research Nurse|