The role of Eph-ephrin signaling in antiangiogenic therapy-mediated resistance and metastasis
MetadataShow full item record
Resistance to antiangiogenic therapies in the treatment of metastatic renal cell carcinoma (RCC) remains a major clinical challenge. However, since the primary target of antiangiogenic therapy is the non-malignant vascular cells, it is unclear whether drug resistance stems from the tumor or host-stroma. It is possible that the tumor and stroma interact (and 'react') together in response to antiangiogenic treatment to promote resistance and may explain putative 'rebound' metastasis when therapy has stopped. In this regard, membrane-bound erythropoietin-producing hepatocellular receptor tyrosine kinase class A2 (EphA2) may be of potential interest. EphA2 plays a crucial role in embryonic development, patterning of the vasculature, and is overexpressed in multiple malignant cancers including breast, prostate, brain and lung cancer. The exact mechanism of EphA2 in cancer progression, however, remains unclear as it possibly functions as an oncogene as well as a tumor suppressor, depending on the ligand independent and ligand depended signaling by ephrin-A1, respectively.