The present invention provides the isolation and cloning of WWOX, a novel WW domain-containing protein mapping to human chromosome 16q23.3 24.1, a region frequently affected in several cancers. This gene encodes a tumor suppressor with apoptotic functions. The invention provides WWOX nucleic acid- and polypeptide-based cancer therapies. The invention also provides methods for cancer detection, diagnosis and prognosis involving WWOX nucleic acids and polypeptides.