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Review

For Better or Worse: The Potential for Dose Limiting the On-Target Toxicity of PI 3-Kinase Inhibitors

1
Department of Molecular Medicine and Pathology, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand
2
Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand
*
Author to whom correspondence should be addressed.
Biomolecules 2019, 9(9), 402; https://doi.org/10.3390/biom9090402
Received: 25 July 2019 / Revised: 15 August 2019 / Accepted: 21 August 2019 / Published: 22 August 2019
(This article belongs to the Special Issue Phosphoinositide 3-kinase, a Field in Transition)
The hyper-activation of the phosphoinositide (PI) 3-kinase signaling pathway is a hallmark of many cancers and overgrowth syndromes, and as a result, there has been intense interest in the development of drugs that target the various isoforms of PI 3-kinase. Given the key role PI 3-kinases play in many normal cell functions, there is significant potential for the disruption of essential cellular functions by PI 3-kinase inhibitors in normal tissues; so-called on-target drug toxicity. It is, therefore, no surprise that progress within the clinical development of PI 3-kinase inhibitors as single-agent anti-cancer therapies has been slowed by the difficulty of identifying a therapeutic window. The aim of this review is to place the cellular, tissue and whole-body effects of PI 3-kinase inhibition in the context of understanding the potential for dose limiting on-target toxicities and to introduce possible strategies to overcome these. View Full-Text
Keywords: cancer; cell signaling; on-target drug toxicity; metabolism; PI 3-kinase inhibition cancer; cell signaling; on-target drug toxicity; metabolism; PI 3-kinase inhibition
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MDPI and ACS Style

Buchanan, C.M.; Lee, K.L.; Shepherd, P.R. For Better or Worse: The Potential for Dose Limiting the On-Target Toxicity of PI 3-Kinase Inhibitors. Biomolecules 2019, 9, 402. https://doi.org/10.3390/biom9090402

AMA Style

Buchanan CM, Lee KL, Shepherd PR. For Better or Worse: The Potential for Dose Limiting the On-Target Toxicity of PI 3-Kinase Inhibitors. Biomolecules. 2019; 9(9):402. https://doi.org/10.3390/biom9090402

Chicago/Turabian Style

Buchanan, Christina M.; Lee, Kate L.; Shepherd, Peter R. 2019. "For Better or Worse: The Potential for Dose Limiting the On-Target Toxicity of PI 3-Kinase Inhibitors" Biomolecules 9, no. 9: 402. https://doi.org/10.3390/biom9090402

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Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

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