title: Novel targeted system to deliver chemotherapeutic drugs to EphA2-expressing cancer cells.
abstract: The efficacy of anticancer drugs is often limited by their systemic toxicities and adverse side effects. We report that the EphA2 receptor is overexpressed preferentially in several human cancer cell lines compared to normal tissues and that an EphA2 targeting peptide (YSAYPDSVPMMS) can be effective in delivering anticancer agents to such tumors. Hence, we report on the synthesis and characterizations of a novel EphA2-targeting agent conjugated with the chemotherapeutic drug paclitaxel. We found that the peptide-drug conjugate is dramatically more effective than paclitaxel alone at inhibiting tumor growth in a prostate cancer xenograft model, delivering significantly higher levels of drug to the tumor site. We believe these studies open the way to the development of a new class of therapeutic compounds that exploit the EphA2 receptor for drug delivery to cancer cells.
authors.affiliation: Cancer Research Center, Sanford-Burnham Medical Research Institute, 10901 N. Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: Si
authors.initials: S
authors.lastname: Wang
authors.forename: William J
authors.initials: WJ
authors.lastname: Placzek
authors.forename: John L
authors.initials: JL
authors.lastname: Stebbins
authors.forename: Sayantan
authors.initials: S
authors.lastname: Mitra
authors.forename: Roberta
authors.initials: R
authors.lastname: Noberini
authors.forename: Mitchell
authors.initials: M
authors.lastname: Koolpe
authors.forename: Ziming
authors.initials: Z
authors.lastname: Zhang
authors.forename: Russell
authors.initials: R
authors.lastname: Dahl
authors.forename: Elena B
authors.initials: EB
authors.lastname: Pasquale
authors.forename: Maurizio
authors.initials: M
authors.lastname: Pellecchia
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D016503:Drug Delivery Systems; D004354:Drug Screening Assays, Antitumor; D042783:Endothelial Cells / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D012333:RNA, Messenger / Q000378:metabolism; D036104:Receptor, EphA2 / Q000235:genetics / Q000378:metabolism*; D014183:Transplantation, Heterologous
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D009842:Oligopeptides; D012333:RNA, Messenger; D036104:Receptor, EphA2; D017239:Paclitaxel