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Review
. 2020 Aug 18;13(1):114.
doi: 10.1186/s13045-020-00944-9.

Targeting EphA2 in cancer

Ta Xiao  1 , Yuhang Xiao  2 , Wenxiang Wang  3   4 , Yan Yan Tang  4 , Zhiqiang Xiao  5 , Min Su  6   7
Affiliations
Review

Targeting EphA2 in cancer

Ta Xiao et al. J Hematol Oncol. .

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.

Keywords: Cancer; EphA2 receptor; Ephrin A1; Target; Therapy.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Historical development and breakthroughs in targeting EphA2 in cancer
Fig. 2
Fig. 2
Expression and biological pathways linked with EphA2. The interaction of cell-membrane-bound EphA2 with ephrin A1 induces forward or reverse signals in the corresponding cells. Under normal conditions, cell–cell contacts allow EphA2 to interact with ephrin A1, which induces EphA2 phosphorylation and activates its downstream signaling. Tyrosine phosphorylation of EphA2 promotes the generation of a complex with c-Cbl, subsequently induces EphA2 degradation. This leads to suppression of ECM attachment, cell proliferation, cell migration, and angiogenesis. In the malignant state, loss of cell–cell contacts induces receptor-ligand interaction and degradation of EphA2. In addition, tyrosine phosphorylation of EphA2 could be rapidly reversed by the phosphatase LMW-PTP, further leading to the overexpression and accumulation of unphosphorylated form of EphA2. This leads to promotion of ECM attachment, cell proliferation, cell migration, and angiogenesis
Fig. 3
Fig. 3
Targeting EphA2 in cancer. EphA2’s expression patterns and functional relevance in malignancies make this protein an attractive therapeutic target in cancer. Accordingly, EphA2 overexpression has been targeted with several approaches such as decrease EPHA2 expression, promote EphA2 degradation, block endogenous EphA2 activation, EphA2 as drug delivery target, EphA2-based immunotherapy, and EphA2-based combination therapeutics
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References

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