Reduction of Circulating Cancer Cells and Metastases in Breast-Cancer Models by a Potent EphA2-Agonistic Peptide–Drug Conjugate
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EphA2 overexpression has been associated with metastasis in multiple cancer types, including melanomas and ovarian, prostate, lung, and breast cancers. We have recently proposed the development of peptide–drug conjugates (PDCs) using agonistic EphA2-targeting agents, such as the YSA peptide or its optimized version, 123B9. Although our studies indicated that YSA– and 123B9–drug conjugates can selectively deliver cytotoxic drugs to cancer cells in vivo, the relatively low cellular agonistic activities (i.e., the high micromolar concentrations required) of the agents toward the EphA2 receptor remained a limiting factor to the further development of these PDCs in the clinic. Here, we report that a dimeric version of 123B9 can induce receptor activation at nanomolar concentrations. Furthermore, we demonstrated that the conjugation of dimeric 123B9 with paclitaxel is very effective at targeting circulating tumor cells and inhibiting lung metastasis in breast-cancer models. These studies represent an important step toward the development of effective EphA2-targeting PDCs.
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A dimeric 123B9 was able to perform receptor activation at concentrations in the nanomolar range.
“Furthermore, a dimeric 123B9 was able to perform receptor activation at concentrations in the nanomolar range.”
From Tumor microenvironment complexity and therapeutic implications at a glance (2020) · cites this paper as [168]
Dimeric 123B9 conjugation with paclitaxel is useful in combating CTCs and preventing lung metastasis in breast cancer models.
“Additionally, dimeric 123B9 conjugation with paclitaxel is found to be very useful in combating CTCs and preventing the lung metastasis in breast cancer models [168].”
From Tumor microenvironment complexity and therapeutic implications at a glance (2020) · cites this paper as [168]
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“Copyright (2017), American Chemical Society paclitaxel is found to be very useful in combating CTCs and preventing the lung metastasis in breast cancer models [168] .”
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- Authors
- Salem, A. F., Wang, S., Billet, S., Chen, J.-F., Udompholkul, P., Gambini, L., Baggio, C., Tseng, H.-R., Posadas, E. M., Bhowmick, N. A., & Pellecchia, M.
- Affiliations
- University of California, Riverside (US)
- Sanford Burnham Prebys Medical Discovery Institute (US)
- Cedars-Sinai Medical Center (US)
- University of California, Los Angeles (US)
- Corresponding author
- Pellecchia, Maurizio
- ORCID
- Venue
- Journal of Medicinal Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2018-02-22
- Volume
- 61
- Issue
- 5
- Pages
- 2052-2061
- ISSN
- 0022-2623 (ISSN-L)
- 1520-4804
- PMC
- PMC5907794
- OpenAlex
- W2789116588
- Cited by
- 68
- References
- 67
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 10 · 2023: 8 · 2022: 10 · 2021: 9 · 2020: 12 · 2019: 5 · 2018: 5
- FWCI
- 2.59
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Journal of Medicinal Chemistry (publishedVersion, other-oa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (CA149668, CA168517)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chemical Synthesis and Analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- EphA2, peptide-drug conjugates, receptor dimerization, paclitaxel, circulating tumor cells, lung metastasis, breast cancer, receptor activation
- MeSH terms
- Animals, Antineoplastic Agents, Breast Neoplasms, Humans, Neoplastic Cells, Circulating, Neoplasm Metastasis, Peptides, Drug Delivery Systems, Paclitaxel, Receptor, EphA2, Mice
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