期刊
FRONTIERS IN ONCOLOGY
卷 4, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2014.00170
关键词
T-cell acute lymphoblastic leukemia; NOTCH1; cyclins; cyclin-dependent kinases; PI3K/AKT/mTOR; PI3K pathway inhibitors; BRD4; bromodomain inhibitors
类别
资金
- Leukemia and Lymphoma Society (LLS)
- William Lawrence and Blanche Hughes Foundation
- Children's Leukemia Research Association
- Fondazione Umberto Veronesi
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.
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