The discovery and development, by members of this NCDDG, of biodegradable and biocompatible controlled release polymers has enabled us to bypass the limitations of the blood-brain and expose the growing brain tumor to high drug concentrations for extended intervals. This approach can effectively administered current and rationally designed new drugs and biological agents. The local, prolonged release of drugs at the site of tumor growth exposes the tumor to high levels of the drug, minimizes systemic exposure and toxicity, and thus reduces health care costs. Program 1 (Brem) will investigate the effectiveness and safety of the best formulations of controlled-release drug delivery for local treatment of brain tumors. Program 2 (Langer) will provide polymer formulations for the selected agents. Program 3 (Saltzman) will construct mathematical models for predicting drug distribution and clearance in the brain. Program 4 (Colvin) will develop chemotherapy agents appropriate for incorporation into polymers for local therapy and design new agents. Program 5 (Pardoll) will polymer delivery of cytokines to develop brain tumor vaccines. Core B (Vincek) will provide polymers prepared with new methods and develop the scale-up and purification of the polymers. The programs of this NCDDG have been working together as a cohesive, collaborative group. Our productivity is reflected in a number of new discoveries by this group which has led to over 236 publications during the past 4 years, most of which involve interactions among the programs. This cooperative effort has allowed us to design and carry out a series of pre-clinical studies to evaluate this new, potentially, curative, cancer treatment, and resulted in the first approval in 23 years by the FDA of a new treatment for brain tumors. 28 additional clinical trials are currently underway based on our research findings. The true promise of this approach, however, will only be fulfilled if additional funding is approved to fully explore and develop this new approach to the treatment of cancer. The NCI is funding a separate U01 for a Hopkins Clinical Consortium to support Phase I testing of the polymers developed in this NCDDG. With ongoing support and participation of the NCI we can continue to interact synergistically and develop fully the promise of this new approach, which will significantly change the outcome for patients with malignant gliomas.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19CA052857-14
Application #
6633037
Study Section
Special Emphasis Panel (ZCA1-SRRB-K (M1))
Program Officer
Wolpert, Mary K
Project Start
2000-09-19
Project End
2005-04-30
Budget Start
2003-05-01
Budget End
2004-04-30
Support Year
14
Fiscal Year
2003
Total Cost
$1,278,774
Indirect Cost
Name
Johns Hopkins University
Department
Neurology
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Gabikian, Patrik; Tyler, Betty M; Zhang, Irma et al. (2014) Radiosensitization of malignant gliomas following intracranial delivery of paclitaxel biodegradable polymer microspheres. J Neurosurg 120:1078-85
Tyler, Betty; Wadsworth, Scott; Recinos, Violette et al. (2011) Local delivery of rapamycin: a toxicity and efficacy study in an experimental malignant glioma model in rats. Neuro Oncol 13:700-9
Slager, Joram; Tyler, Betty; Shikanov, Ariella et al. (2009) Local controlled delivery of anti-neoplastic RNAse to the brain. Pharm Res 26:1838-46
Pradilla, Gustavo; Wang, Paul P; Gabikian, Patrik et al. (2006) Local intracerebral administration of Paclitaxel with the paclimer delivery system: toxicity study in a canine model. J Neurooncol 76:131-8
Sampath, Prakash; Rhines, Laurence D; DiMeco, Francesco et al. (2006) Interstitial docetaxel (taxotere), carmustine and combined interstitial therapy: a novel treatment for experimental malignant glioma. J Neurooncol 80:9-17
Legnani, Federico G; Pradilla, Gustavo; Thai, Quoc-Anh et al. (2006) Lactacystin exhibits potent anti-tumor activity in an animal model of malignant glioma when administered via controlled-release polymers. J Neurooncol 77:225-32
Li, Yawen; Ho Duc, Hong Linh; Tyler, Betty et al. (2005) In vivo delivery of BCNU from a MEMS device to a tumor model. J Control Release 106:138-45
Sorg, Brian S; Peltz, Cathryn D; Klitzman, Bruce et al. (2005) Method for improved accuracy in endogenous urea recovery marker calibrations for microdialysis in tumors. J Pharmacol Toxicol Methods 52:341-9
Li, Yawen; Shawgo, Rebecca S; Tyler, Betty et al. (2004) In vivo release from a drug delivery MEMS device. J Control Release 100:211-9
Grossi, Peter M; Ochiai, Hidenobu; Archer, Gary E et al. (2003) Efficacy of intracerebral microinfusion of trastuzumab in an athymic rat model of intracerebral metastatic breast cancer. Clin Cancer Res 9:5514-20

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