Physics

Internal medicine

Notch signaling pathway

Bioinformatics

Biology

Optics

Cancer

Crosstalk

Angiogenesis

Targeted therapy

Signal transduction

Computational biology

Cancer research

Clinical trial

Genetics

Medicine

Nature Reviews Drug Discovery

Notch signalling is involved in many aspects of cancer biology, including angiogenesis, tumour immunity and the maintenance of cancer stem-like cells. In addition, Notch can function as an oncogene and a tumour suppressor in different cancers and in different cell populations within the same tumour. Despite promising preclinical results and early-phase clinical trials, the goal of developing safe, effective, tumour-selective Notch-targeting agents for clinical use remains elusive. However, our continually improving understanding of Notch signalling in specific cancers, individual cancer cases and different cell populations, as well as crosstalk between pathways, is aiding the discovery and development of novel investigational Notch-targeted therapeutics. The Notch pathway plays multiple complex roles in cancer, exerting oncogenic or tumour-suppressive actions depending on the context. Here Miele and colleagues provide an overview of current understanding of the functions of Notch in cancer, highlighting key implications for the development of Notch-targeting therapeutics. Agents in clinical development and emerging therapeutic strategies are highlighted.

Targeting Notch in oncology: the path forward