The role of oncogenic Notch2 signaling in cancer: a novel therapeutic target

Deregulated Notch signaling is a key factor thought to facilitate the stem-like proliferation of cancer cells, thereby facilitating disease progression. Four subtypes of Notch receptor have been described to date, with each playing a distinct role in cancer development and progression, therefore warranting a careful and comprehensive examination of the targeting of each receptor subtype in the context of oncogenesis. Clinical efforts to translate the DAPT, which blocks Notch signaling, have been unsuccessful due to a combination of serious gastrointestinal side effects and a lack of complete blocking efficacy. There is therefore a clear need to identify better therapeutic strategies for targeting and manipulating Notch signaling. Notch2 is a Notch receptor that is commonly overexpressed in a range of cancers, and which is linked to a unique oncogenic mechanism. Successful efforts to block Notch2 signaling will depend upon doing so both efficiently and specifically in patients. As such, in the present review we will explore the role of Notch2 signaling in the development and progression of cancer, and we will assess agents and strategies with the potential to effectively disrupt Notch2 signaling and thereby yield novel cancer treatment regimens.