title: A thermally targeted c-Myc inhibitory polypeptide inhibits breast tumor growth.
abstract: 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. We have developed a thermally responsive polypeptide, based on the sequence of Elastin-like polypeptide (ELP), that inhibits breast cancer cell proliferation by blocking the activity of the oncogenic protein c-Myc. Following systemic administration, the ELP - delivered c-Myc inhibitory peptide was targeted to tumors using focused hyperthermia, and significantly reduced tumor growth in an orthotopic mouse model of breast cancer. This work provides a new modality for targeted delivery of a specific oncogene inhibitory peptide, and this strategy may be expanded for delivery of other therapeutic peptides or small molecule drugs.
authors.affiliation: Department of Biochemistry, The University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA; Cancer Institute, The University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA. Electronic address: gbidwell@umc.edu.
authors.forename: Gene L
authors.initials: GL
authors.lastname: Bidwell
authors.affiliation: Cancer Institute, The University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA; Department of Neurosurgery, The University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA; Department of Neurobiology and Anatomical Sciences, The University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA. Electronic address: eperkins@umc.edu.
authors.forename: Eddie
authors.initials: E
authors.lastname: Perkins
authors.affiliation: Department of Biochemistry, The University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA; Cancer Institute, The University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA. Electronic address: draucher@umc.edu.
authors.forename: Drazen
authors.initials: D
authors.lastname: Raucher
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D010455:Peptides / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016271:Proto-Oncogene Proteins c-myc / Q000037:antagonists & inhibitors*
chemical_list: C489427:MYC protein, human; D010455:Peptides; D016271:Proto-Oncogene Proteins c-myc