The present invention provides compositions and methods of using the EPHB2 gene or its related signaling pathways to detect, prognosticate, assess the risk of, prevent, or treat cancers. Cancers amenable to the present invention include, but are not limited to, prostate cancer, breast cancer, and neuroblastoma. In one aspect, the present invention provides compositions which comprise an agent capable of eradicating or alleviating an abnormality in the EPHB2 gene or its related signaling pathways. This abnormality may cause or contribute to the development or progression of cancers. In another aspect, the present invention provides methods comprising detecting an abnormality in the EPHB2 gene or its related signaling pathways. The presence or absence of such an abnormality is indicative of the risk or disease status of cancer in a person of interest.