Therapeutic potential of PI3K signaling in distinct entities of B-cell lymphoma

Expert Rev Hematol. 2019 Dec;12(12):1053-1062. doi: 10.1080/17474086.2019.1676716. Epub 2019 Oct 11.

Abstract

Introduction: Aberrant phosphatidylinositide 3-kinase (PI3K) signaling drives survival and proliferation of malignant B-cells of different lymphoma entities. Thus, inhibition of PI3K isoforms represents a novel and promising therapeutic approach for the treatment of patients with B-cell lymphomas.Areas covered: Here the authors provide an overview about the PI3K signaling pathway as well as available preclinical and clinical results of different PI3K inhibitors in both indolent and aggressive lymphoma entities.Expert opinion: PI3K inhibitors have shown to be efficacious in different entities of B-cell lymphoma, at this stage particularly in relapsed/refractory settings. However, responses of PI3K inhibitors widely vary among different lymphomas. Additionally, especially infectious and immune-mediated toxicities limit their use at this stage. Thus, the decision to use PI3K inhibitors needs to be balanced between the potential efficacy and associated toxicities as well as the availability of other therapeutic options. Future research might eventually lead to the stratification of patients according to the specific oncogenic addictions of the underlying lymphoma. Additionally, PI3K inhibitors will need to be combined with other therapeutic agents for more specific and effective treatment regimens.

Keywords: B-cell lymphoma; PI3K inhibition; PI3K signaling pathway.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Humans
  • Lymphoma, B-Cell* / drug therapy
  • Lymphoma, B-Cell* / enzymology
  • Lymphoma, B-Cell* / immunology
  • Neoplasm Proteins* / antagonists & inhibitors
  • Neoplasm Proteins* / immunology
  • Neoplasm Proteins* / metabolism
  • Phosphatidylinositol 3-Kinases* / immunology
  • Phosphatidylinositol 3-Kinases* / metabolism
  • Phosphoinositide-3 Kinase Inhibitors / therapeutic use*
  • Signal Transduction / drug effects*

Substances

  • Antineoplastic Agents
  • Neoplasm Proteins
  • Phosphoinositide-3 Kinase Inhibitors