Lessons, Challenges and Future Therapeutic Opportunities for PI3K Inhibition in CLL.

Chronic lymphocytic leukemia (CLL) shows constitutive phosphatidylinositol 3-kinase (PI3K) activation resulting from aberrant regulation of the B-cell receptor (BCR) signaling. PI3K inhibitors have been evaluated in CLL therapy, bringing a new treatment opportunity for patients with this disease. Despite the proven therapeutic efficacy, the use of approved PI3K inhibitors is limited by severe immune-mediated toxicities and given the availability of other more tolerable agents. This article reviews the relevance of PI3K signaling and pharmacologic inhibition in CLL. Data on efficacy and toxicity of PI3K inhibitors are also presented, as well as strategies for overcoming barriers for their clinical use in CLL treatment.