Research

Inhibition of PI3K signaling Spurs new therapeutic opportunities in inflammatory/autoimmune diseases and hematological malignancies


Reference:

Foster, J.G., Blunt, M.D., Carter, E. and Ward, S.G., 2012. Inhibition of PI3K signaling Spurs new therapeutic opportunities in inflammatory/autoimmune diseases and hematological malignancies. Pharmacological Reviews, 64 (4), pp. 1027-1054.

Related documents:

This repository does not currently have the full-text of this item.
You may be able to access a copy if URLs are provided below. (Contact Author)

Official URL:

http://dx.doi.org/10.1124/pr.110.004051

Related URLs:

Abstract

The phosphoinositide 3-kinase/mammalian target of rapamycin/protein kinase B (PI3K/ mTOR/Akt) signaling pathway is central to a plethora of cellular mechanisms in a wide variety of cells including leukocytes. Perturbation of this signaling cascade is implicated in inflammatory and autoimmune disorders as well as hematological malignancies. Proteins within the PI3K/mTOR/Akt pathway therefore represent attractzts for therapeutic intervention. There has been a remarkable evolution of PI3K inhibitors in the past 20 years from the early chemical tool compounds to drugs that are showing promise as anticancer agents in clinical trials. The use of animal models and pharmacological tools has expanded our knowledge about the contribution of individual class I PI3K isoforms to immune cell function. In addition, class II and III PI3K isoforms are emerging as nonredundant regulators of immune cell signaling revealing potentially novel targets for disease treatment. Further complexity is added to the PI3K/mTOR/Akt pathway by a number of novel signaling inputs and feedback mechanisms. These can present either caveats or opportunities for novel drug targets. Here, we consider recent advances in 1) our understanding of the contribution of individual PI3K isoforms to immune cell function and their relevance to inflammatory/autoimmune diseases as well as lymphoma and 2) development of small molecules with which to inhibit the PI3K pathway. We also consider whether manipulating other proximal elements of the PI3K signaling cascade (such as class II and III PI3Ks or lipid phosphatases) are likely to be successful in fighting off different immune diseases.

Details

Item Type Articles
CreatorsFoster, J.G., Blunt, M.D., Carter, E. and Ward, S.G.
DOI10.1124/pr.110.004051
Related URLs
URLURL Type
http://www.scopus.com/inward/record.url?scp=84867091296&partnerID=8YFLogxKUNSPECIFIED
DepartmentsFaculty of Science > Pharmacy & Pharmacology
Research CentresCentre for Regenerative Medicine
RefereedYes
StatusPublished
ID Code33269

Export

Actions (login required)

View Item