title: Duvelisib: a phosphoinositide-3 kinase δ/γ inhibitor for chronic lymphocytic leukemia.
abstract: Frontline chemotherapy is successful against chronic lymphocytic leukemia (CLL), but results in untoward toxicity. Further, prognostic factors, cytogenetic anomalies, and compensatory cellular signaling lead to therapy resistance or disease relapse. Therefore, for the past few years, development of targeted therapies is on the rise. PI3K is a major player in the B-cell receptor (BCR) signaling axis, which is critical for the survival and maintenance of B cells. Duvelisib, a PI3K δ/γ dual isoform specific inhibitor that induces apoptosis and reduces cytokine and chemokine levels in vitro, holds promise for CLL. Areas covered: Herein, we review PI3K isoforms and their inhibitors in general, and duvelisib in particular; examine literature on preclinical investigations, pharmacokinetics and clinical studies of duvelisib either as single agent or in combination, for patients with CLL and other lymphoid malignancies. Expert opinion: Duvelisib targets the PI3K δ isoform, which is necessary for cell proliferation and survival, and γ isoform, which is critical for cytokine signaling and pro-inflammatory responses from the microenvironment. In phase I clinical trials, duvelisib as a single agent showed promise for CLL and other lymphoid malignancies. Phase II and III trials of duvelisib alone or in combination with other agents are ongoing.
authors.affiliation: a Department of Experimental Therapeutics , The University of Texas MD Anderson Cancer Center , Houston , TX , USA.
authors.forename: Hima V
authors.initials: HV
authors.lastname: Vangapandu
authors.affiliation: b Department of Leukemia , The University of Texas MD Anderson Cancer Center , Houston , TX , USA.
authors.forename: Nitin
authors.initials: N
authors.lastname: Jain
authors.affiliation: a Department of Experimental Therapeutics , The University of Texas MD Anderson Cancer Center , Houston , TX , USA.
authors.forename: Varsha
authors.initials: V
authors.lastname: Gandhi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D058534:Class I Phosphatidylinositol 3-Kinases; D058544:Class Ib Phosphatidylinositol 3-Kinase; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology / Q000627:therapeutic use*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011687:Purines / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D007546:Isoquinolines; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011687:Purines; C586691:duvelisib; D058534:Class I Phosphatidylinositol 3-Kinases; D058544:Class Ib Phosphatidylinositol 3-Kinase; C497132:PIK3CB protein, human; C546760:PIK3CG protein, human
keywords: CLL; PI3K; duvelisib; leukemia; therapy