The Eph receptor tyrosine kinases and their ephrin ligands play significant roles in cancer development and progression through bidirectional signaling. Eph receptors and ephrins are expressed in cancer cells and tumor blood vessels, influencing tumor growth, invasion, angiogenesis, and metastasis. However, their signaling is complex, with both promoting and inhibiting effects on tumorigenicity. Eph receptors and ephrins are involved in various cellular processes, including cell morphology, adhesion, migration, and invasion, and their dysregulation can contribute to cancer progression. Eph signaling can be modulated by various factors, including epigenetic changes, mutations, and interactions with other signaling pathways. Eph receptors represent promising therapeutic targets in cancer, with strategies under evaluation to target the Eph system for cancer therapy. Eph signaling can promote tumor suppression by inhibiting oncogenic pathways, but it can also contribute to tumor promotion in certain contexts. The expression of Eph receptors and ephrins varies among cancer types and stages, with some showing increased expression while others show decreased expression. Eph receptors and ephrins are also present in the tumor microenvironment, where they influence tumor properties by enabling aberrant cell-cell communication. Eph mutations may also play a role in cancer pathogenesis. The Eph system is involved in tumor angiogenesis, and its regulation is critical for tumor growth and metastasis. Eph receptors and ephrins are promising therapeutic targets in cancer, with various strategies under evaluation to interfere with their tumor-promoting effects or enhance their tumor-suppressing effects. Targeting Eph receptors and ephrins may provide new approaches for cancer therapy, with potential applications in drug delivery, imaging, and immunotherapy. Overall, the Eph system is a complex and multifaceted signaling network that plays a crucial role in cancer biology and may represent a promising target for cancer treatment.The Eph receptor tyrosine kinases and their ephrin ligands play significant roles in cancer development and progression through bidirectional signaling. Eph receptors and ephrins are expressed in cancer cells and tumor blood vessels, influencing tumor growth, invasion, angiogenesis, and metastasis. However, their signaling is complex, with both promoting and inhibiting effects on tumorigenicity. Eph receptors and ephrins are involved in various cellular processes, including cell morphology, adhesion, migration, and invasion, and their dysregulation can contribute to cancer progression. Eph signaling can be modulated by various factors, including epigenetic changes, mutations, and interactions with other signaling pathways. Eph receptors represent promising therapeutic targets in cancer, with strategies under evaluation to target the Eph system for cancer therapy. Eph signaling can promote tumor suppression by inhibiting oncogenic pathways, but it can also contribute to tumor promotion in certain contexts. The expression of Eph receptors and ephrins varies among cancer types and stages, with some showing increased expression while others show decreased expression. Eph receptors and ephrins are also present in the tumor microenvironment, where they influence tumor properties by enabling aberrant cell-cell communication. Eph mutations may also play a role in cancer pathogenesis. The Eph system is involved in tumor angiogenesis, and its regulation is critical for tumor growth and metastasis. Eph receptors and ephrins are promising therapeutic targets in cancer, with various strategies under evaluation to interfere with their tumor-promoting effects or enhance their tumor-suppressing effects. Targeting Eph receptors and ephrins may provide new approaches for cancer therapy, with potential applications in drug delivery, imaging, and immunotherapy. Overall, the Eph system is a complex and multifaceted signaling network that plays a crucial role in cancer biology and may represent a promising target for cancer treatment.