The role of Eph receptors in cancer and how to target them: novel approaches in cancer treatment

Expert Opin Investig Drugs. 2020 Jun;29(6):567-582. doi: 10.1080/13543784.2020.1762566. Epub 2020 May 22.


Introduction: Erythropoietin-producing human hepatocellular (Eph) receptors are among the largest family of tyrosine kinases that are divided into two classes: EphA and EphB receptors. Over the past two decades, their role in cancer has become more evident.

Areas covered: There is a need for new anticancer treatments and more insight in the emerging role of Eph receptors in cancer. Molecular mechanisms underlying the pro-tumorigenic effects of Eph receptors could be exploited for future therapeutic strategies. This review describes the variability in expression levels and different effects on oncogenic and tumor suppressive downstream signaling of Eph receptors in various cancer types, and the small molecules, antibodies and peptides that target these receptors.

Expert opinion: The complexity of Eph signaling is a challenge for the definition of clear targets for cancer treatment. Nevertheless, numerous drugs that target EphA2 and EphB4 are currently in clinical trials. However, some Eph targeted drugs also inhibit other tyrosine kinases, so it is unclear to what extent the targeting of Eph receptors contributes to their efficacy. Future research is warranted for an improved understanding of the full network in which Eph receptors function. This will be critical for the improvement of the anticancer effects of drugs that target the Eph receptors.

Keywords: Anti-cancer drugs; Eph receptors; cancer; expression levels; mechanisms; receptor tyrosine kinases.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Drug Development
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Molecular Targeted Therapy
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Neoplasms / pathology
  • Protein Kinase Inhibitors / pharmacology*
  • Receptors, Eph Family / antagonists & inhibitors*
  • Receptors, Eph Family / genetics
  • Receptors, Eph Family / metabolism


  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Receptors, Eph Family