Eph receptor tyrosine kinases play critical functions during development, in the formation of tissue and organ borders, and the vascular and neural systems. Uniquely among
tyrosine kinases, their activities are controlled by binding to membrane-bound
ligands, called
ephrins. Ephs and
ephrins generally have a low expression in adults, functioning mainly in tissue homeostasis and plasticity, but are often overexpressed in
cancers, where they are especially associated with undifferentiated or progenitor cells, and with tumour development, vasculature, and invasion. Mutations in
Eph receptors also occur in various tumour types and are suspected to promote tumourigenesis. Ephs and
ephrins have the capacity to operate as both tumour promoters and tumour suppressors, depending on the circumstances. They have been demonstrated to impact tumour cell proliferation, migration, and invasion in vitro, as well as tumour development, angiogenesis, and
metastases in vivo, making them potential therapeutic targets. However, successful development of
therapies will require detailed understanding of the opposing roles of Ephs in various
cancers. In this review, we discuss the variations in Eph expression and functions in a variety of
malignancies. We also describe the multiple strategies that are currently available to target them in tumours, including preclinical and clinical development.