Notch Signaling: A Potential Therapeutic Target for Hematologic Malignancies

• Published in: Critical reviews in eukaryotic gene expression Vol. 26; no. 3; p. 239
• Main Authors: Gao, Lingbao, Yuan, Keyu, Ding, Wei, Lin, Mei
• Format: Journal Article
• Language: English
• Published: United States 2016
• Subjects: Amyloid Precursor Protein Secretases - antagonists & inhibitors; Antibodies, Monoclonal - pharmacology; Antibodies, Monoclonal - therapeutic use; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Hematologic Neoplasms - drug therapy; Hematologic Neoplasms - metabolism; Humans; Receptors, Notch - antagonists & inhibitors; Signal Transduction - drug effects; Transcription Factors - antagonists & inhibitors
• ISSN: 1045-4403
• DOI: 10.1615/CritRevEukaryotGeneExpr.2016016587

Notch signaling is a well-conserved cell-fate determining factor in embryo development, and the dyregulation of this signaling is frequently observed in many types of cancers, including hematological malignancies. In this review, we briefly describe the Notch signaling pathway, and we primarily focus on the relationship between Notch and hematological malignancies. We also discuss the clinical development of promising agents including γ-secretase inhibitors (GSIs) and monoclonal antibodies (mAbs). Complete response has been observed among patients with T-cell acute lymphoblastic leukemia (T-ALL) when treated with GSIs. Furthermore, a recent study has suggested that targeting Zmiz1, a direct, selective cofactor of Notch1, rather than targeting Notch directly, maybe helpful to reduce the current target-related toxicities. Taken together, we summarize the role of Notch signaling in hematological malignancies and discuss the treatment strategies for these diseases through targeting Notch signaling.