title: PI3K signaling pathway in normal B cells and indolent B-cell malignancies.
abstract: In chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphomas (NHLs), B-cell receptor signaling leads to activation of the phosphatidylinositol 3-kinase (PI3K) pathway. Idelalisib, a PI3Kδ inhibitor was approved in 2014 by the US Food and Drug Administration (FDA) in combination with rituximab for the treatment of patients with CLL for whom single-agent rituximab would be considered appropriate and as a single agent for patients with relapsed small lymphocytic lymphoma (SLL) and relapsed follicular lymphoma (FL). Following its approval, several trials investigating various PI3Kδ inhibitors as single agents or in combination with chemoimmunotherapy or other molecular targeted agents in CLL and indolent NHL (iNHL) have uncovered some severe autoimmune related toxicities. This review discusses and summarizes the biologic basis and the clinical experience of the PI3Kδ inhibitors in indolent B-cell malignancies.
authors.affiliation: Medical Oncology Service, National Cancer Institute, National Institutes of Health, Bethesda, MD; Women's Malignancies Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD. Electronic address: georgios.pongas@nih.gov.
authors.forename: Georgios
authors.initials: G
authors.lastname: Pongas
authors.affiliation: Georgetown University Hospital, Lombardi Comprehensive Cancer Center, Washington, DC.
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Cheson
mesh_terms: D001402:B-Lymphocytes / Q000502:physiology*; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000209:etiology; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000209:etiology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000502:physiology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors
keywords: Chronic lymphocytic leukemia; Idelalisib; Indolent non-Hodgkin lymphoma; Leukemia; Lymphoma; PI3K