title: New Approaches to Target T-ALL.
abstract: Acute lymphoblastic leukemia is the most common malignancy in children. Although it is now curable in 80-90% of cases, patients with T-cell acute lymphoblastic leukemia (T-ALL) experience a higher frequency of induction failure and early relapse. Despite aggressive treatment approaches, including transplantation and new salvage regimens, most children with relapsed T-ALL will not be cured. As such, we are in need of new targeted therapies for the disease. Recent advances in the molecular characterization of T-ALL have uncovered a number of new therapeutic targets. This review will summarize recent advancements in the study of inhibiting the NOTCH1, PI3K-AKT, and Cyclin D3:CDK4/6 pathways as therapeutic strategies for T-ALL. We will focus on pre-clinical studies supporting the testing of small-molecule inhibitors targeting these proteins and the rationale of combination therapies. Moreover, epigenetic approaches to modulate T-ALL are rapidly emerging. Here, we will discuss the data supporting the role of bromodomain and extra-terminal bromodomain inhibitors in human T-ALL.
authors: Department of Pediatric Oncology, Dana-Farber Cancer Institute , Boston, MA , USA ; Division of Hematology/Oncology, Boston Children's Hospital , Boston, MA , USA ; Hematology and Bone Marrow Transplantation Unit, University of Perugia , Perugia , Italy.
authors: Giovanni
authors: G
authors: Roti
authors: Department of Pediatric Oncology, Dana-Farber Cancer Institute , Boston, MA , USA ; Division of Hematology/Oncology, Boston Children's Hospital , Boston, MA , USA ; Broad Institute of Harvard and Massachusetts Institute of Technology , Cambridge, MA , USA.
authors: Kimberly
authors: K
authors: Stegmaier
keywords: BRD4; NOTCH1; PI3K pathway inhibitors; PI3K/AKT/mTOR; T-cell acute lymphoblastic leukemia; bromodomain inhibitors; cyclin-dependent kinases; cyclins