The role of Dickkopf family in cancers: from Bench to Bedside.

Numerous epidemiological studies indicate that cancer will be responsible for millions of deaths in one year. Although multiple therapeutic strategies exist, and vast research efforts are being focused on developing newer and better regimens, cancer-related morbidity and mortality remain high. Metastasis and recurrence are prominent causes of treatment failure in cancers. Moreover, early diagnosis and treatment initiation are difficult to achieve in clinical practice. Fortunately, targeted therapy, which exerts its function at the molecular level, has proved to be greatly beneficial in several human diseases including cancers. The Wnt signaling pathway is a crucial regulator of embryogenesis and development in humans, and its dysfunction has been implicated in the incidence and development of cancers and other diseases. The Dickkopf family (Dkks) is a widely studied Wnt signaling pathway antagonist and plays multiple roles in human physiological and pathological process through both Wnt pathway-dependent and -independent manners. However, the precise roles of Dkks in tumorigenesis and the causal mechanisms have not been clearly elucidated. We discuss the pleiotropic roles of Dkks, with a specific focus on the underlying mechanisms, in cancer biology. We review recent literature to explore the potential use of Dkks as a tumor diagnosis biomarker and therapeutic target.