Viewing the Eph receptors with a focus on breast cancer heterogeneity

Aberrant expression of different family members of the Eph/ephrin system, which comprises the Eph receptors (Ephs) and their ligands (ephrins), has been implicated in various malignancies including breast cancer. The latter presents as a heterogeneous disease with diverse molecular, morphologic and clinical behavior signatures. This review reflects the existing Eph/ephrin literature while focusing on breast cancer heterogeneity. Hormone positive, HER2 positive and triple negative breast cancer (TNBC) cell lines, xenografts/mutant animal models and patient samples are examined separately as, in humans, they represent entities with differences in prognosis and treatment. EphA2, EphB4 and EphB6 are the members most extensively studied in breast cancer. Existing research points to the potential use of various Eph/ephrin members as biomarkers for assessing prognosis and selecting the most suitable therapeutic strategies in variable clinical scenarios, also for overcoming drug resistance, in the era of breast cancer heterogeneity.