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Synergistic induction of cell death in haematological malignancies by combined phosphoinositide-3-kinase and BET bromodomain inhibition.

Tinsley, S; Meja, K; Shepherd, C; Khwaja, A; (2015) Synergistic induction of cell death in haematological malignancies by combined phosphoinositide-3-kinase and BET bromodomain inhibition. British Journal of Haematology , 170 (2) pp. 275-278. 10.1111/bjh.13283. Green open access

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Abstract

There has been a marked increase in the development of targeted therapies for the treatment of malignant disease. Responses may be compromised by the presence of pre-existing or treatment-induced resistance mechanisms. The phosphoinositide- 3-kinase (PI3K) pathway has been a major focus of drug development due to its function as a key regulator of cell growth and survival. PI3Ks may be dysregulated by mechanisms including mutations of the negative regulator phosphatase and tensin homologue (PTEN), of regulatory and catalytic subunits and of upstream regulators, such as tyrosine kinases and the RAS family (Fruman & Rommel, 2014). Key targets of PI3K include the serine/threonine kinase AKT and the mechanistic target of rapamycin (MTOR) pathway.

Type: Article
Title: Synergistic induction of cell death in haematological malignancies by combined phosphoinositide-3-kinase and BET bromodomain inhibition.
Open access status: An open access version is available from UCL Discovery
DOI: 10.1111/bjh.13283
Publisher version: http://dx.doi.org/10.1111/bjh.13283
Language: English
Additional information: This is the peer reviewed version of the following article: Tinsley, S; Meja, K; Shepherd, C; Khwaja, A; (2015) Synergistic induction of cell death in haematological malignancies by combined phosphoinositide-3-kinase and BET bromodomain inhibition. Br J Haematol, which has been published in final form at: http://dx.doi.org/10.1111/bjh.13283. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
Keywords: MYC, JQ1, PI3K, apoptosis, bromodomain containing 4
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
URI: http://discovery.ucl.ac.uk/id/eprint/1462080
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