Thermally Targeted Delivery of a c-Myc Inhibitory Peptide In Vivo Using Elastin-like Polypeptide
Annual summary rept. 2 Sep 2008-2 Sep 2009
MISSISSIPPI UNIV MEDICAL CENTER JACKSON
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Although surgical resection with adjuvant chemotherapy andor radiotherapy are used to treat breast tumors, normal tissue tolerance, development of metastases, and inherent tumor resistance to radiation or chemotherapy can hinder a successful outcome. Therefore, it is necessary to consider alternative targeted therapeutic approaches for adjuvant therapy that would significantly reduce undesired side effects in normal tissues. This proposal describes a thermally responsive polypeptide CPP-ELP-H1 that inhibits breast cancer cell proliferation by blocking the activity of the oncogenic protein c-Myc. The objective of the proposed research is to demonstrate that these genetically engineered polypeptides can be targeted to the tumor site by applying local hyperthermia and can inhibit tumor growth in an animal model. During the first year of this training program, we have used radio-labeled polypeptides to demonstrate that thermal targeting can, in fact, be used to enhance the accumulation of an ELP-based c-Myc inhibitory polypeptide at the tumor site, and we have collected promising tumor reduction data using a lead c-Myc inhibitory polypeptide. Several modifications have been made to the research plan, including altering the way the polypeptide is labeled and adding an additional animal model, and future experiments will complete the proposed aims of determining the optimum CPP for thermal targeting and demonstrating tumor reduction efficacy with the lead CPP-ELP-H1 polypeptide.
- Medicine and Medical Research