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Targeting EphA2 in cancer.

ABSTRACT: Eph receptors and the corresponding Eph receptor-interacting (ephrin) ligands jointly constitute a critical cell signaling network that has multiple functions. The tyrosine kinase EphA2, which belongs to the family of Eph receptors, is highly produced in tumor tissues, while found at relatively low levels in most normal adult tissues, indicating its potential application in cancer treatment. After 30?years of investigation, a large amount of data regarding EphA2 functions have been compiled. Meanwhile, several compounds targeting EphA2 have been evaluated and tested in clinical studies, albeit with limited clinical success. The present review briefly describes the contribution of EphA2-ephrin A1 signaling axis to carcinogenesis. In addition, the roles of EphA2 in resistance to molecular-targeted agents were examined. In particular, we focused on EphA2's potential as a target for cancer treatment to provide insights into the application of EphA2 targeting in anticancer strategies. Overall, EphA2 represents a potential target for treating malignant tumors.

SUBMITTER: Xiao T

PROVIDER: S-EPMC7433191 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Targeting EphA2 in cancer.

Xiao Ta T Xiao Yuhang Y Wang Wenxiang W Tang Yan Yan YY Xiao Zhiqiang Z Su Min M

Journal of hematology & oncology 20200818 1

Eph receptors and the corresponding Eph receptor-interacting (ephrin) ligands jointly constitute a critical cell signaling network that has multiple functions. The tyrosine kinase EphA2, which belongs to the family of Eph receptors, is highly produced in tumor tissues, while found at relatively low levels in most normal adult tissues, indicating its potential application in cancer treatment. After 30 years of investigation, a large amount of data regarding EphA2 functions have been compiled. Mea ...[more]

PMID: 32811512

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Emerging strategies for EphA2 receptor targeting for cancer therapeutics.

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Effective Tumor Targeting by EphA2-Agonist-Biotin-Streptavidin Conjugates.

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miR-302b inhibits tumorigenesis by targeting EphA2 via Wnt/ ?-catenin/EMT signaling cascade in gastric cancer.

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Inhibition of angiogenesis by leflunomide via targeting the soluble ephrin-A1/EphA2 system in bladder cancer.

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| S-EPMC5784165 | biostudies-literature

Structure-activity relationship analysis of peptides targeting the EphA2 receptor.

Project description:The EphA2 receptor tyrosine kinase has emerged as a promising new therapeutic target in cancer because of its high level of expression in tumors. EphA2-specific antibodies have been used to deliver drugs and toxins to tumor cells, leading to inhibition of tumor growth and metastatic dissemination. We previously identified two related peptides, YSA and SWL, that selectively bind to the ligand-binding domain of EphA2 but not other Eph receptors and could therefore be useful as selective targeting agents. Here we characterize the two peptides and a series of derivatives. On the basis of systematic amino acid replacements, only five YSA residues appear to be critical for high-affinity receptor binding. Furthermore, a peptide comprising only the first five residues of YSA retains selectivity for EphA2. Similar to ephrin-A1, the physiological ligand for EphA2, both YSA and SWL activate EphA2 and inhibit downstream oncogenic signaling pathways in PC3 cancer cells. The two peptides and derivatives are quite stable in conditioned cell culture medium and show promise for delivering drugs and imaging agents to EphA2-expressing tumors.

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