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

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 signaling pathway
• PI3K inhibition

Article highlights

• Oncogenic PI3K signaling is a major molecular mechanism driving cell survival, cell proliferation and inhibition of apoptosis of malignant B-cells.

• Inhibition of PI3K signaling represents a valuable therapeutic strategy in the treatment of patients with different lymphoma entities.

• PI3K inhibitors differ as they target diverse PI3K-isoforms.

• Relevant side effects of PI3K inhibitors include bacterial and opportunistic infections as well as immune-mediated toxicities.

Declaration of interest

G Lenz received research grants from AQUINOX, AstraZeneca, Bayer, Celgene, Gilead, Janssen, Morphosys, Novartis, Roche, and Verastem. GL received honoraria from AstraZeneca, Bayer, BMS, Celgene, Gilead, Janssen, Morphosys, Novartis, and Roche. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or conflict with the subject matter or materials discussed in this manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.