EPHA3 as a novel therapeutic target in the hematological malignancies

The Eph receptors are the largest family of tyrosine kinases and are of increasing interest in developmental therapeutics. Their unique method of interaction with their ligands, the ephrins, via bidirectional signaling, and their variable expression in different tissues are well documented. Ephs are upregulated in, and critical to, embryological processes, most notably development of the neurological system. They are central in many processes involving cell motility and adhesion. Recent findings on elevated expression of Eph receptors in human malignancies as well as in stem cell environments are of particular interest. With increasing focus on molecularly targeted anticancer therapies, exploration of the potential of Eph receptors as therapeutic targets in both solid and hematologic malignancies has begun. The most promising of the Eph receptors in this regard is EPHA3, which is overexpressed in many hematologic malignancies. Preclinical data support the value of pursuing this target for further development, and lead compounds are now entering the clinic.