Abstract

We currently have an active protocol for preclinical pharmacokinetic analysis of new agents. Over the past year, we have further developed a close working relationship with the Pharmacology and Experimental Therapeutics Section of the POB to partner in pharmacologic investigations of new agents. We have successfully obtained new agents from intramural and extramural sources to investigate, and are developing biomarkers in the preclinical setting.In general, for an antitumor agent to have an effect, you need: -an active agent, -Delivered to tumor -Present at tumor site in its active form -Effective concentrations -Long enough period of time -Tolerability at doses necessary to achieve above -For targeted therapy, need to know if the target is presentWe are developing methods to further investigate the mechanisms of action of agents currently in clinical trials, and investigate biomarkers or surrogate markers of drug activity and tumor response. We are developing a new animal model for brain microdialysis.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC011340-03
Application #
8553116
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2012
Total Cost
$237,394
Indirect Cost

  Institution

Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Nellan, Anandani; McCully, Cynthia M Lester; Cruz Garcia, Rafael et al. (2018) Improved CNS exposure to tocilizumab after cerebrospinal fluid compared to intravenous administration in rhesus macaques. Blood 132:662-666
Nellan, Anandani; Rota, Christopher; Majzner, Robbie et al. (2018) Durable regression of Medulloblastoma after regional and intravenous delivery of anti-HER2 chimeric antigen receptor T cells. J Immunother Cancer 6:30
League-Pascual, James C; Lester-McCully, Cynthia M; Shandilya, Shaefali et al. (2017) Plasma and cerebrospinal fluid pharmacokinetics of select chemotherapeutic agents following intranasal delivery in a non-human primate model. J Neurooncol 132:401-407
Miyahara, Hiroaki; Yadavilli, Sridevi; Natsumeda, Manabu et al. (2017) The dual mTOR kinase inhibitor TAK228 inhibits tumorigenicity and enhances radiosensitization in diffuse intrinsic pontine glioma. Cancer Lett 400:110-116
Shah, Nirali N; Cole, Diane E; Lester-McCully, Cynthia M et al. (2016) Plasma and cerebrospinal fluid pharmacokinetics of vincristine and vincristine sulfate liposomes injection (VSLI, marqibo®) after intravenous administration in Non-human primates. Invest New Drugs 34:61-5
Cole, Diane E; Lester-McCully, Cynthia M; Widemann, Brigitte C et al. (2015) Plasma and cerebrospinal fluid pharmacokinetics of the Akt inhibitor, perifosine, in a non-human primate model. Cancer Chemother Pharmacol 75:923-8
Lester McCully, Cynthia M; Bacher, John; MacAllister, Rhonda P et al. (2015) Development of a cerebrospinal fluid lateral reservoir model in rhesus monkeys (Macaca mulatta). Comp Med 65:77-82
McCully, Cynthia M; Pastakia, Devang; Bacher, John et al. (2013) Model for concomitant microdialysis sampling of the pons and cerebral cortex in rhesus macaques (Macaca mulatta). Comp Med 63:355-60
Marcus, Leigh; Murphy, Robert; Fox, Elizabeth et al. (2012) The plasma and cerebrospinal fluid pharmacokinetics of the platinum analog satraplatin after intravenous administration in non-human primates. Cancer Chemother Pharmacol 69:247-52