Notch signaling as a therapeutic target for acute lymphoblastic leukemia. (3rd April 2018)

• Record Type: Journal Article
• Authors: Bellavia, Diana; Palermo, Rocco; Felli, Maria Pia; Screpanti, Isabella; Checquolo, Saula
• Is Part Of: Expert opinion on therapeutic targets. Volume 22:Number 4(2018:Apr.)
• Page Start: 331
• Page End: 342
• Publication Date: 2018-04-03
• Subjects: ALL -- microenvironment -- natural compounds -- Notch -- targeted therapies; Drugs -- Research -- Periodicals; 615.072
• DOI: 10.1080/14728222.2018.1451840
• Languages: English
• ISSNs: 1744-7631

Abstract

ABSTRACT: Introduction : Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy. Although the therapy of ALL has significantly improved, the heterogeneous genetic landscape of the disease often causes relapse, which is difficult to treat. Achieving a positive outcome for patients with relapsed or refractory ALL remains a challenging issue. The high prevalence of NOTCH-activating mutations in T-cell acute lymphoblastic leukemia (T-ALL) and the central role of NOTCH signaling in regulating cell survival and growth of ALL provide a rationale for the development of Notch signaling-targeted strategies in this disease. Therapeutic alternatives with effective anti-leukemic potential and low toxicity are needed. Areas covered : This review provides an overview of the currently available drugs directly or indirectly targeting Notch signaling in ALL. Besides considering the known Notch targeting approaches, such as γ-secretase inhibitors (GSIs) and Notch inhibiting antibodies (mAbs), currently in clinical trials, we focus on the recent insights into the molecular mechanisms underlying the Notch signaling regulation in ALL. Expert opinion : Novel drugs targeting specific steps of Notch signaling or intersecting pathways could improve the efficiency of the conventional hematological cancers therapies. Further studies are required to translate the new findings into future clinical applications.