Novel Targeted System To Deliver Chemotherapeutic Drugs to EphA2-Expressing Cancer Cells
Open accessAbstract
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.
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Wang et al. developed a peptide-drug conjugate using EphA2 agonists, YSA peptide or its enhanced version 123B9.
“In a recent study, Wang et al. developed a peptide–drug conjugate (PDCs) using EphA2 agonists, YSA peptide or its enhanced version, 123B9.”
From Tumor microenvironment complexity and therapeutic implications at a glance (2020) · cites this paper as [166]
The Introduction and Results describe YSA as an EphA2-activating peptide and report the development of a YSA–paclitaxel conjugate. Our copy does not identify 123B9 or report a conjugate made with that enhanced peptide, so that part of the attribution is unsupported. (LLM, conf=0.88)
Experimental — accuracy not yet measuredYSA- and 123B9-drug conjugates could selectively transport cytotoxic drugs to cancer cells in vivo.
“Their studies suggested that YSA– and 123B9– drug conjugates could selectively transport cytotoxic drugs to cancer cells in vivo [166, 167].”
From Tumor microenvironment complexity and therapeutic implications at a glance (2020) · cites this paper as [166]
The Results section (‘YSA-PTX targets tumors in vivo’) reports greater paclitaxel delivery to mouse tumor xenografts with YSA-PTX than with free paclitaxel, supporting the YSA portion. This paper does not address 123B9 conjugates, so it does not support that part of the sentence. (LLM, conf=0.87)
Experimental — accuracy not yet measured
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“Their studies suggested that YSA-and 123B9-drug conjugates could selectively transport cytotoxic drugs to cancer cells in vivo [166, 167] .”
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Self-citationTarget Hopping as a Useful Tool for the Identification of Novel EphA2 Protein–Protein Antagonists
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Targefrin: A Potent Agent Targeting the Ligand Binding Domain of EphA2
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Self-citationRetractedPinpointed Stimulation of EphA2 Receptors via DNA-Templated Oligovalence
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Gemcitabine Integrated Nano-Prodrug Carrier System
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The EphA2 and cancer connection: potential for immune-based interventions
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Ephrin or not? Six tough questions on Eph targeting
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Therapeutic Targeting of Pancreatic Cancer via EphA2 Dimeric Agonistic Agents
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The Functions of EphA1 Receptor Tyrosine Kinase in Several Tumors
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The Quest for an Effective Treatment for an Intractable Cancer
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Effective Tumor Targeting by EphA2-Agonist-Biotin-Streptavidin Conjugates
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Self-citationTargeting the EphA2 pathway: could it be the way for bone sarcomas?
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Harnessing the Power of Eph/ephrin Biosemiotics for Theranostic Applications
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Differential association of EphA2 intracellular regions in biased signaling
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BindingDB Entry 50015688: Targefrin: A Potent Agent Targeting the Ligand Binding Domain of EphA2.
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- Authors
- Wang, S., Placzek, W. J., Stebbins, J. L., Mitra, S., Noberini, R., Koolpe, M., Zhang, Z., Dahl, R., Pasquale, E. B., & Pellecchia, M.
- Affiliations
- Sanford Burnham Prebys Medical Discovery Institute (US)
- Corresponding author
- Pellecchia, Maurizio
- ORCID
- Venue
- Journal of Medicinal Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2012-02-27
- Volume
- 55
- Issue
- 5
- Pages
- 2427-2436
- ISSN
- 0022-2623 (ISSN-L)
- 1520-4804
- PMC
- PMC3299084
- OpenAlex
- W2054891903
- Cited by
- 94
- References
- 51
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 5 · 2023: 3 · 2022: 7 · 2021: 6 · 2020: 10 · 2019: 6 · 2018: 8 · 2017: 4 · 2016: 8 · 2015: 9 · 2014: 9 · 2013: 7 · 2012: 4
- FWCI
- 4.15
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Journal of Medicinal Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (P01CA138390, CA138390)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chemical Synthesis and Analysis
- Keywords
- EphA2, targeted drug delivery, peptide-drug conjugates, paclitaxel, tumor targeting, prostate cancer, tumor xenografts, receptor overexpression, anticancer drug toxicity
- MeSH terms
- Animals, Antineoplastic Agents, Phytogenic, Cell Survival, Drug Screening Assays, Antitumor, Enzyme-Linked Immunosorbent Assay, Humans, Neoplasm Transplantation, Oligopeptides, RNA, Messenger, Transplantation, Heterologous, Drug Delivery Systems, Mice, SCID, Paclitaxel, Receptor, EphA2, Endothelial Cells, Cell Line, Tumor, Mice
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