Our Science – Balis Website

Frank M. Balis, M.D.

Pediatric Oncology Branch Head, Pharmacology and Experimental Therapeutics Section Senior Investigator Building 10, Room 3-2571 NCI-Bethesda Bethesda, MD 20982 Phone:   301-496-0085 Fax:   301-496-9020 E-Mail:   balisf@nih.gov

Biography

Dr. Balis received his B.S. in zoology from the University of North Carolina in 1971 and his M.D. from Vanderbilt University in 1975. He completed a pediatric residency at Vanderbilt Children's Hospital in 1978 followed by 4 years of fellowship training in pediatric hematology/oncology at the Children's Hospital in Seattle and the Fred Hutchinson Cancer Research Center. Dr. Balis came to the Pediatric Oncology Branch in 1982 as a clinical associate and became a senior investigator in the branch in 1988. He is board certified in pediatrics and pediatric hematology/oncology.

Research

The research objective of the Pharmacology and Experimental Therapeutics Section is to develop innovative therapeutic approaches for childhood cancers through the clinical development of novel investigational agents and the study of the clinical pharmacology of new and existing anticancer drugs. An integrated approach incorporating preclinical studies in in vitro and animal models as well as clinical trials and clinical pharmacokinetic studies is utilized in the development of new agents. An emphasis is placed on studying the central nervous system pharmacology of new agents and on the development of new treatment approaches for central nervous system tumors. For new systemic anticancer drugs, analytical techniques to assay drug concentrations are developed and preclinical pharmacokinetic studies are performed in a nonhuman primate model, which is highly predictive of drug disposition in humans. Methods for measuring tissue and tumor drug concentrations using microdialysis are being investigated. Cytotoxicity studies in pediatric tumor cell lines are used to define therapeutic concentrations, schedule dependence, and the applicability and spectrum of activity of the new agent against pediatric tumors. These preclinical studies guide in the design of the initial phase I and II clinical trials and pharmacokinetic studies in children with refractory cancer. New agents studied in preclinical models and in clinical trials include standard cytotoxic agents as well as noncytotoxic agents such as molecularly targeted agents, differentiating agents, and agents that modulate anticancer drugs (e.g., p-glycoprotein inhibitors). Systemically administered drugs that penetrate the blood-brain barrier are identified and targeted for studies in patients with brain tumors. We are also evaluating agents that can alter blood-brain barrier permeability, such as lobradamil, and we have developed several new agents that can be administered intrathecally for the treatment of meningeal tumor.

Studies of the clinical pharmacology of anticancer drugs used in the treatment of children with cancer focus on the pharmacokinetics and pharmacodynamics of standard drugs. Drug concentrations are measured by a variety of techniques, including high-pressure liquid chromatography, gas chromatography, radioimmunoassays, and enzyme inhibition assays. Preclinical pharmacokinetic studies are performed in animal models, and clinical pharmacokinetic/pharmacodynamic studies are performed in children treated in NCI clinical trials of standard anticancer drugs. Mathematical models are developed to describe drug disposition and relate drug concentrations to measures of toxicity and response. Our section also collaborates with other CCR branches and has performed pharmacokinetic studies in adults treated with both investigational and standard agents. The studies of existing agents are designed to identify more rational approaches to their use by developing limited sampling strategies to simplify drug monitoring and defining pharmacodynamic correlates that relate drug concentrations to toxicity or efficacy of the drug. The latter approach should lead to more individualized, adaptive dosing methods that can improve efficacy and reduce the toxicity of anticancer and antiretroviral agents.

This section is also investigating fluorescent pteridine-based nucleoside analogs that can be site-specifically incorporated into DNA oligonucleotides with a DNA synthesizer. These novel fluorophores are highly fluorescent and have chemical structures that resemble purines. The fluorescent properties of a series of these compounds are being characterized and potential applications are being investigated. These new fluorophores are promising probes for the study of protein/DNA interactions because they are not attached externally and they do not appear to disrupt the tertiary structure of DNA. Applications for the fluorophores include an assay for akyltransferase activity and as hybridization probes where they have the potential to replace radioactive probes.

This page was last updated on 9/25/2008.