2017
DOI: 10.1080/13543784.2017.1384815
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Abstract: Introduction Phosphatidylinositol-3-kinase (PI3K) inhibitors comprise a novel class of agents that are effective for the treatment of chronic lymphocytic leukemia (CLL) and indolent non-Hodgkin lymphoma (iNHL). The demonstrated efficacy and subsequent FDA approval of the prototypical PI3Kδ inhibitor idelalisib has led to development of multiple compounds targeting this pathway. Areas Covered We review the hypothesized therapeutic mechanisms of PI3K inhibitors, including abrogation of tonic signaling from the… Show more

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Cited by 65 publications
(47 citation statements)
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“…Because of its importance in immune signaling, PI3K␦ is considered an important therapeutic target in the treatment of inflammation and autoimmunity (Okkenhaug et al, 2002). Based on its high expression in leukocytes, it is also a target in hematological malignancies (Lampson and Brown, 2017), including chronic lymphocytic leukemia (Furman et al, 2014). Compared with leukocytes, PI3K␦ is also expressed at moderate levels in neurons (Eickholt et al, 2007;Low et al, 2014), and we demonstrate here that PI3K␦ inhibition blocks APP anterograde trafficking in hippocampal neurons.…”
Section: Discussionmentioning
confidence: 61%
“…Because of its importance in immune signaling, PI3K␦ is considered an important therapeutic target in the treatment of inflammation and autoimmunity (Okkenhaug et al, 2002). Based on its high expression in leukocytes, it is also a target in hematological malignancies (Lampson and Brown, 2017), including chronic lymphocytic leukemia (Furman et al, 2014). Compared with leukocytes, PI3K␦ is also expressed at moderate levels in neurons (Eickholt et al, 2007;Low et al, 2014), and we demonstrate here that PI3K␦ inhibition blocks APP anterograde trafficking in hippocampal neurons.…”
Section: Discussionmentioning
confidence: 61%
“…Our findings of the importance of the PI3K/AKT pathway in the HSC stress response also have important clinical implications. Several isoform-selective PI3K inhibitors are approved to treat lymphoid malignancies (39,40). For instance, idelalisib, which selectively targets p110δ, is used to treat chronic lymphocytic leukemia (CLL) and indolent non-Hodgkin's lymphoma.…”
Section: Discussionmentioning
confidence: 99%
“…might lead to a situation highly advantageous for immune escape, but vulnerable to combination of metabolic and immunotherapies. 196,197 This could be due, at least in part, to the largely cytostatic effect of these drugs and to the cases mutational status not accounted for. Whether specific subtypes of DLBCL could particularly benefit from this treatment is currently unknown.…”
Section: Targeting Metabolic Vulnerabilitiesmentioning
confidence: 99%
“…The PI3K pathway is implicated not only in lymphomas but almost every other cancer, leading to the development of many PI3K inhibitors with distinct isoform selectivity. Despite the pathway being altered, response rates in aggressive DLBCL as well as transformed FL were moderate for PI3K inhibitors 196,197. Despite the pathway being altered, response rates in aggressive DLBCL as well as transformed FL were moderate for PI3K inhibitors 196,197.…”
mentioning
confidence: 99%