National Cancer Institute, USA
Pediatric Neuro-Oncology Section
My research focuses on optimizing clinical trial design by pre-clinically evaluating pharmacokinetics and CNS drug delivery in an animal model. This information is used to determine ideal route of drug delivery (systemic, intrathecal, intranasal, convection-enhanced delivery) to achieve biologically effective dosing at the tumor site.
Our animal models have chronically indwelling IV and CSF access, facilitating serial assessment of drug exposures in CSF fluid and the blood compartment simultaneously, allowing for multiple sample collection over time for PK studies. This model has been used to determine CSF and extracellular fluid penetration and toxicities of agents in development for patients with CNS tumors.
Tumor type: all children's brain tumors; special focus on brainstem glioma.
Existing collaborations relevant to drug delivery
Publications relevant to drug delivery
League-Pascual JC, Lester-McCully CM, Shandilya S, Ronner L, Rodgers L, Cruz R, Peer CJ, Figg WD, Warren KE. Plasma and cerebrospinal fluid pharmacokinetics of select chemotherapeutic agents following intranasal delivery in a non-human primate model. Journal Neuro-Oncology 2017, 132(3):401-407.
Nailor A, Walker DA, Jacques TS, Warren KE, Brem H, Kearns PR, Greenwood J, Penny JI, Pilkington GJ, Carcaboso AM, Fleischhack G, Macarthur D, Slavc I, Meijer L, Gill S, Lowis S, van Vuurden DG, Pearl MS, Clifford SC, Morrissy S, Ivanov DP, Beccaria K, Gilbertson RJ, Straathof K, Green JJ, Smith S, Rahman R, Kilday JP. “Highlights of Children with Cancer UK’s Workshop on Drug Delivery in Paediatric Brain Tumours.” Ecancermedicalscience 2016; 10:630.
MacAllister RP, McCully CML, Bacher J, Thomas ML, Cruz R, Wangari S, Warren KE. “Development of a minimally invasive lumbar port model for cerebrospinal fluid collection in rhesus monkeys (Macaca mulatta).” Comparative Medicine 2016; 66(4):349-352.
Cole DE, Lester-McCully CM, Widemann BC, Warren KE. Plasma and cerebrospinal fluid pharmacokinetics of the Akt inhibitor, perifosine, in a non-human primate model. Cancer Chemotherapy and Pharmacology, 2015; 75(5): 923-928.
McCully CM, Bacher J, Pung MacAllister R, Steffen-Smith EA, Saleem K, Thomas III ML, Cruz R, Warren KE. Development of a cerebrospinal fluid lateral reservoir model in rhesus monkeys (Macaca mulatta). Comp Med, 2015; 65(1): 1-6.
Chittiboina P, Heiss JD, Warren KE, Lonser RR. Magnetic resonance imaging properties of convective delivery in diffuse intrinsic pontine gliomas. J Neurosurg Pediatr 2014;13(3):276-282. PMID: 24410126.
Warren KE. Novel therapeutic delivery approaches in development for pediatric gliomas. CNS Oncol 2013; 2(5): 427-435. PMID: 24511389.
McCully CM, Pastakia D, Bacher J, Thomas ML 3rd, Steffen-Smith EA, Saleem K, Murphy RF, Walbridge S, Brinster L, Widemann BC,Warren KE. Model for concomitant microdialysis sampling of the pons and cerebral cortex in rhesus macaques (Macaca mulatta). Comp Med 2013; 63(4):355-360. PMID: 24209972.
Marcus L, Murphy R, Fox E, McCully C, Cruz R, Warren KE, Meyer T, McNiff E, Balis FM, Widemann BC. The plasma and cerebrospinal fluid pharmacokinetics of the platinum analog satraplatin after intravenous administration in non-human primates. Cancer Chemother Pharmacol. 2012; 69(1): 247-252.
Heiss J, Jamshidi A, Martin S, Wolters P, Warren KE, Lonser RR. “Phase I trial of convection enhanced delivery of IL-13 Pseudomonas toxin in diffuse intrinsic pontine glioma patients".
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