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: Si Wang, William J Placzek, John L Stebbins, Sayantan Mitra, Roberta Noberini, Mitchell Koolpe, Ziming Zhang, Russell Dahl, Elena B Pasquale, Maurizio Pellecchia
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 55 Issue 5 Pg. 2427-36 (Mar 08 2012) ISSN: 1520-4804 [Electronic] United States
• PMID: 22329578 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Antineoplastic Agents, Phytogenic
• Oligopeptides
• RNA, Messenger
• Receptor, EphA2
• Paclitaxel

Topics

• Animals
• Antineoplastic Agents, Phytogenic (administration & dosage, chemistry, pharmacokinetics)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Drug Delivery Systems
• Drug Screening Assays, Antitumor
• Endothelial Cells (metabolism)
• Enzyme-Linked Immunosorbent Assay
• Humans
• Mice
• Mice, SCID
• Neoplasm Transplantation
• Oligopeptides (chemical synthesis, chemistry)
• Paclitaxel (administration & dosage, chemistry, pharmacokinetics)
• RNA, Messenger (metabolism)
• Receptor, EphA2 (genetics, metabolism)
• Transplantation, Heterologous