Naslov
Thermally Targeted Delivery of a C-Myc Inhibitory Peptide to Breast Tumors in Vivo Using Elastin-Like Polypeptide

Autori
Raucher, Dražen ; Bidwell III, Gene L ; Perkins, Eddie

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research / - , 2011

Skup
102nd Annual Meeting of the American Association for Cancer Research

Mjesto i datum
Orlando (FL), Sjedinjene Američke Države, 02.04.2011. - 06.04.2011

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Targeted drug delivery; c-Myc; Peptides; Hyperthermia

Sažetak
Although surgical resection with adjuvant chemotherapy and/or 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. We have developed a thermally responsive polypeptide (CPP-ELP-H1) that inhibits breast cancer cell proliferation by blocking the activity of the oncogenic protein c-Myc. When administered IV into mice bearing orthotopic, syngeneic breast tumors, CPP-ELP-H1 exhibited a long plasma half life and accumulated in tumor tissue. The tumor levels of the CPP-ELP delivered H1 peptide were enhanced when hyperthermia was applied to the tumor site. Daily administration (7 days) of CPP-ELP-H1 followed by tumor heating induced over 70% reduction in tumor volume compared to unheated controls or controls lacking the H1 inhibitory peptide. This work provides a new modality for targeted delivery of a specific oncogene inhibitor. In addition to the peptide’s intrinsic tumor targeting due to its oncogene inhibition, ELP can be physically targeted to the tumor site by application of external hyperthermia. Specific targeting of the proposed therapeutic polypeptides by local hyperthermia to breast tumors or to areas of potential metastasis following tumor resection would increase specificity and efficacy of treatment and reduce the cytotoxicity in normal tissues

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti

POVEZANOST RADA