Wnt signaling in cancer: therapeutic targeting of Wnt signaling beyond β-catenin and the destruction complex

Cancer: A search for safer signaling targets More effective treatments for cancer could be developed by targeting signaling pathway regulators that are expressed solely in cancer cells. Disruption to a major signaling pathway known as Wnt, which is involved in processes including cell proliferation, tissue homeostasis and tissue regeneration, is now recognized as a significant contributor to the development of certain cancers. Jae-Il Park and Youn-Sang Jung at the University of Texas MD Anderson Cancer Center, Houston, USA, reviewed recent research into Wnt signaling in cancer and possible therapies. Scientists have developed Wnt inhibitors for cancer treatment, but these have detrimental side effects including skeletal degeneration and abdominal pain. New studies suggest there are Wnt signaling regulators that are specifically expressed in cancer cells, which may prove to be more effective drug targets than blocking Wnt signaling as a whole. Wnt/beta-catenin signaling is implicated in many physiological processes, including development, tissue homeostasis, and tissue regeneration. In human cancers, Wnt/beta-catenin signaling is highly activated, which has led to the development of various Wnt signaling inhibitors for cancer therapies. Nonetheless, the blockade of Wnt signaling causes side effects such as impairment of tissue homeostasis and regeneration. Recently, several studies have identified cancer-specific Wnt signaling regulators. In this review, we discuss the Wnt inhibitors currently being used in clinical trials and suggest how additional cancer-specific regulators could be utilized to treat Wnt signaling-associated cancer.