Drazen Raucher
Professor
Molecular Cancer Therapeutics
Ph.D., Molecular Biophysics, 1995, Institute of Molecular Biophysics,
Florida State University, Tallahassee, Florida
Postdoctoral Studies, 1995-1999, Duke University Medical Center
Assistant Research Professor, 1999-2000, Duke University Medical Center
Assistant Research Professor, 2001-2002, Duke University
Assistant Professor, 2002-2007, University of Mississippi Medical Center
Associate Professor, 2007-2010, University of Mississippi Medical Center
Professor, 2010-present, University of Mississippi Medical Center
Contact Information
2500 N State St, Room 320
Jackson, MS 39216
Phone: 601-815-6765
Email: draucher@umc.edu
Research Interests
- Thermally targeted biopolymer drug carriers
- Drug-delivery systems in oncology
- Therapeutic peptides
Research Synopsis
Due to the severe side effects and limited efficacy of many current chemotherapeutics for the treatment of cancer, new agents and drug delivery systems are needed. Peptide therapeutics are a promising new strategy for targeted cancer therapy because of the ease of peptide design and the specificity of peptides for their targets. However, the utility of peptides is limited by their poor pharmacokinetic parameters in vivo. Our long term goal is to overcome this limitation by developing an approach that allows peptide therapeutics to be delivered specifically to the tumor site. To accomplish this goal we are developing an externally triggered drug delivery system that can selectively deliver therapeutic peptides to solid tumors. The proposed drug carrier is based on the thermally responsive biopolymer elastin-like polypeptide (ELP), which is soluble at physiological temperature, but undergoes a phase transition and aggregates in response to externally applied mild hyperthermia at 40-41 °C. A cell-penetrating peptide (CPP) is conjugated to ELP to facilitate cell entry, and therapeutic peptide is added to inhibit cancer cell proliferation. Such thermally responsive polypeptides are amenable to molecular design and engineering, are easily and inexpensively produced at high purity and quantity, and may be efficiently targeted and adapted to any cell type or tissue. In addition to being passively targeted to the tumor site because of its macromolecular properties, accumulation of ELP carriers may be further enhanced in tumor tissues by focused hyperthermia. Furthermore, an additional level of specificity may be achieved by targeting oncogenic or cell cycle regulatory proteins often functioning aberrantly in cancer cells. This will open the door for the use of an entire class of promising therapeutic molecules with increased tumor specificity and reduced toxicity.
Selected Publications
- Bidwell GL 3rd and Raucher D. Application of thermally responsive polypeptides directed against c-Myc transcriptional function for cancer therapy. Mol. Cancer Ther. 4, 1076-85, 2005.
- Bidwell GL 3rd et al. Targeting a c-Myc Inhibitory Polypeptide to Specific Intracellular Compartments using Cell Penetrating Peptides. J. Control. Release. 135(1), 2-10, 2009.
- Moktan S et al. A thermally responsive biopolymer conjugated to an acidsensitive derivative of paclitaxel stabilizes microtubules, arrests cell cycle, and induces apoptosis. Investigational New Drugs Epub 2010 Oct 12 PMID: 20938714.
- Bidwell GL 3rd et al. Development of Elastin-like polypeptide for thermally-targeted delivery of doxorubicin. Biochem. Pharmacol. 73(5), 620-31, 2007.
- Raucher D and Bidwell GL 3rd. Cell Penetrating Elastin-like Polypeptides for Therapeutic Peptide Delivery. Adv. Drug. Deliv. Rev. 62(15), 1486-96, 2010.
