AUTHOR=Roti Giovanni , Stegmaier Kimberly 

TITLE=New Approaches to Target T-ALL

JOURNAL=Frontiers in Oncology

VOLUME=Volume 4 - 2014

YEAR=2014

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2014.00170

DOI=10.3389/fonc.2014.00170

ISSN=2234-943X

ABSTRACT=Acute lymphoblastic leukemia (ALL) is the most common malignancy in children. Although it is now curable in 80-90% of cases, patients with 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 preclinical 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 BET bromodomain inhibitors in human T-ALL.