ACTIONS OF PI3K-DELTA INHIBITOR, IDELALISIB, AND ITS COMBINATION WITH BENDAMUSTINE IN CHRONIC LYMPHOCYTIC LEUKEMIA

TL;DRAbstract

Class I phosphatidylinositol 3-kinase isoforms (α, β, δ, and γ) play a major role in cancer cell growth and survival. PI3K α and β are most studied. PI3K pathway is highly dysregulated in many cancers and aberrant PI3K signaling is associated with oncogene mutations and disease progression in solid tumors and in hematologic malignancies. Chronic lymphocytic leukemia (CLL) is driven by B-cell receptor (BCR) signaling that promotes B-cell proliferation and survival. PI3K is a critical node in BCR pathway and PI3Kδ has a pivotal role in B-cell development and maintenance and this isoform is over-expressed in many B-cell malignancies, including CLL. Idelalisib is a FDA approved small molecule PI3Kδ inhibitor. Idelalisib promotes apoptosis in CLL by disrupting molecular pathways related to BCR signaling, leukemic migration and signals from the microenvironment. Importantly, idelalisib inhibits BCR-derived PI3K signaling, dampening survival signals. We hypothesized that similar to inhibition

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