Characterization of structurally distinct, isoform-selective phosphoinositide 3'-kinase inhibitors in combination with radiation in the treatment of glioblastoma

Molecular Cancer Therapeutics
Jack S ChenDavid Stokoe

Abstract

The phosphoinositide 3'-kinase (PI3K)-mediated signaling pathway plays a key role in fundamental cellular functions important in normal cellular homeostasis and malignant transformation. Deregulated signaling through this pathway contributes to development of gliomas and their resistance to radiation and chemotherapy. Targeting the PI3K signaling pathway has thus emerged as a promising approach to successful treatment of gliomas. We assessed the radiosensitizing potential of four small-molecule inhibitors that differ in their activities against specific isoforms of the PI3K 110-kDa catalytic subunit (p110). p110alpha inhibitors blocked phosphorylation of both protein kinase B/Akt and S6 in all cell lines examined, effectively decreased cellular proliferation, and produced additive cytotoxic effects in combination with radiation therapy. The p110beta inhibitor exhibited limited biochemical effects and failed to decrease cellular proliferation or viability as either a single agent or in combination with radiation or rapamycin. In vivo studies examining the effects of the p110alpha inhibitor in combination with radiation indicated a significant reduction in tumor growth rate induced by the combined treatment compared with each tre...Continue Reading

References

Sep 1, 1985·International Journal of Radiation Oncology, Biology, Physics·B Fertil, E P Malaise
Nov 1, 1995·Glia·O BöglerW K Cavenee
Dec 2, 1999·Experimental Cell Research·B Vanhaesebroeck, M D Waterfield
Sep 22, 2000·The Biochemical Journal·S P DaviesP Cohen
Sep 3, 2002·Nature Cell Biology·Edward J McManus, Dario R Alessi
Jan 18, 2003·International Journal of Cancer. Journal International Du Cancer·Christopher Y ThomasRobert Wharen
Jun 6, 2003·International Journal of Radiation Oncology, Biology, Physics·Anjali K GuptaW Gillies McKenna
May 15, 2004·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Arnab ChakravartiJay S Loeffler
Mar 1, 2005·Journal of Neuro-oncology·Jean L NakamuraDaphne A Haas-Kogan
Oct 29, 2005·International Journal of Radiation Oncology, Biology, Physics·Alexander R GottschalkDaphne A Haas-Kogan
Nov 17, 2005·Oncogene·Jin Q ChengSanto V Nicosia
Apr 13, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jann N SarkariaC David James
Apr 25, 2006·Biochemical and Biophysical Research Communications·Kanaklata RoyBrendan D Price
May 16, 2006·Cancer Cell·Qi-Wen FanWilliam A Weiss
Mar 28, 2007·Molecular Cell·Yasemin SancakDavid M Sabatini

❮ Previous
Next ❯

Citations

Feb 5, 2013·Cancer Chemotherapy and Pharmacology·Howard A Burris
Sep 17, 2008·Oncogene·T L Yuan, L C Cantley
Jul 23, 2009·Cancer Research·Naseer QayumEric J Bernhard
Jan 21, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Kevin D CourtneyJeffrey A Engelman
Aug 31, 2010·Future Oncology·Sílvia Carvalho, Fernando Schmitt
Feb 12, 2013·Biochimica Et Biophysica Acta·Michal Grzmil, Brian A Hemmings
Jul 19, 2011·Journal of Thyroid Research·Natalie BurrowsGeorg Brabant
May 22, 2009·Expert Opinion on Therapeutic Patents·Francis DumontPierre Bischoff
Jun 2, 2012·Expert Opinion on Drug Discovery·David A ReardonWolfgang Wick
Jul 11, 2009·Expert Opinion on Investigational Drugs·Amancio Carnero
Oct 16, 2012·Biochemical Pharmacology·Luca PersanoGiampietro Viola
Dec 17, 2008·Brain Pathology·Christine K ChengWilliam A Weiss
Oct 8, 2009·International Journal of Cancer. Journal International Du Cancer·Marta López-FauquedJuan A Recio
Nov 10, 2009·International Journal of Radiation Biology·Julie Hamilton, Eric J Bernhard
Oct 15, 2014·Cancer Treatment Reviews·Hanneke StegemanJohan Bussink
May 28, 2010·Blood·Hiroshi IkedaKenneth C Anderson
Sep 17, 2008·Oncogene·C Garcia-Echeverria, W R Sellers
Jan 8, 2014·Oncotarget·Maria Giovanna Francipane, Eric Lagasse
Jan 31, 2014·Journal of Neuro-oncology·Emmanuel ChautardPierre Verrelle
Dec 24, 2010·Oncotarget·Oleg Schmidt-KittlerShibin Zhou
Apr 18, 2009·Molecular Cancer Research : MCR·Romina MaroneMatthias P Wymann

❮ Previous
Next ❯

Related Concepts

Related Feeds

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.

Astrocytes

Astrocytes are glial cells that support the blood-brain barrier, facilitate neurotransmission, provide nutrients to neurons, and help repair damaged nervous tissues. Here is the latest research.

Astrocytes & Neurodegeneration

Astrocytes are important for the health and function of the central nervous system. When these cells stop functioning properly, either through gain of function or loss of homeostatic controls, neurodegenerative diseases can occur. Here is the latest research on astrocytes and neurodegeneration.