PI3K signaling pathway in normal B cells and indolent B-cell malignancies

Georgios Pongas, Bruce D. Cheson

Research output: Contribution to journalReview articlepeer-review

23 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)647-654
Number of pages8
JournalSeminars in Oncology
Volume43
Issue number6
DOIs
StatePublished - Dec 1 2016
Externally publishedYes

Keywords

  • Chronic lymphocytic leukemia
  • Idelalisib
  • Indolent non-Hodgkin lymphoma
  • Leukemia
  • Lymphoma
  • PI3K

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