Targeting the phosphoinositide 3-kinase pathway in hematologic malignancies

Jabbour, Elias, Ottmann, Oliver ORCID: https://orcid.org/0000-0001-9559-1330, Deininger, Michael and Hochhaus, Andreas 2014. Targeting the phosphoinositide 3-kinase pathway in hematologic malignancies. Haematologica 99 (1) , pp. 7-18. 10.3324/haematol.2013.087171

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Abstract

The phosphoinositide 3-kinase pathway represents an important anticancer target because it has been implicated in cancer cell growth, survival, and motility. Recent studies show that PI3K may also play a role in the development of resistance to currently available therapies. In a broad range of cancers, various components of the phosphoinositide 3-kinase signaling axis are genetically modified, and the pathway can be activated through many different mechanisms. The frequency of genetic alterations in the phosphoinositide 3-kinase pathway, coupled with the impact in oncogenesis and disease progression, make this signaling axis an attractive target in anticancer therapy. A better understanding of the critical function of the phosphoinositide 3-kinase pathway in leukemias and lymphomas has led to the clinical evaluation of novel rationally designed inhibitors in this setting. Three main categories of phosphoinositide 3-kinase inhibitors have been developed so far: agents that target phosphoinositide 3-kinase and mammalian target of rapamycin (dual inhibitors), pan-phosphoinositide 3-kinase inhibitors that target all class I isoforms, and isoform-specific inhibitors that selectively target the α, -β, -γ, or -δ isoforms. Emerging data highlight the promise of phosphoinositide 3-kinase inhibitors in combination with other therapies for the treatment of patients with hematologic malignancies. Further evaluation of phosphoinositide 3-kinase inhibitors in first-line or subsequent regimens may improve clinical outcomes. This article reviews the role of phosphoinositide 3-kinase signaling in hematologic malignancies and the potential clinical utility of inhibitors that target this pathway.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > R Medicine (General)
Publisher:	Ferrata Storti Foundation
ISSN:	0390-6078
Date of First Compliant Deposit:	12 December 2016
Date of Acceptance:	4 October 2013
Last Modified:	03 May 2023 21:09
URI:	https://orca.cardiff.ac.uk/id/eprint/96803

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