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Title: Mechanisms of resistance to pi3k inhibitors in cancer: Adaptive responses, drug tolerance and cellular plasticity
Authors: Wright, Sarah Christine Elisabeth
Vasilevski, Natali
Serra, Violeta
Rodon, Jordi
Eichhorn, Pieter Johan Adam 
Keywords: Mechanisms of resistance
PI3K pathway
PI3K pathway inhibitors
Issue Date: 26-Mar-2021
Publisher: MDPI AG
Citation: Wright, Sarah Christine Elisabeth, Vasilevski, Natali, Serra, Violeta, Rodon, Jordi, Eichhorn, Pieter Johan Adam (2021-03-26). Mechanisms of resistance to pi3k inhibitors in cancer: Adaptive responses, drug tolerance and cellular plasticity. Cancers 13 (7) : 1538. ScholarBank@NUS Repository.
Rights: Attribution 4.0 International
Abstract: The phosphatidylinositol?3?kinase (PI3K) pathway plays a central role in the regulation of several signalling cascades which regulate biological processes such as cellular growth, survival, proliferation, motility and angiogenesis. The hyperactivation of this pathway is linked to tumour progression and is one of the most common events in human cancers. Additionally, aberrant activation of the PI3K pathway has been demonstrated to limit the effectiveness of a number of antitumour agents paving the way for the development and implementation of PI3K inhibitors in the clinic. However, the overall effectiveness of these compounds has been greatly limited by inadequate target engagement due to reactivation of the pathway by compensatory mechanisms. Herein, we review the common adaptive responses that lead to reactivation of the PI3K pathway, therapy resistance and potential strategies to overcome these mechanisms of resistance. Furthermore, we highlight the potential role in changes in cellular plasticity and PI3K inhibitor resistance. © 2021 by the author. Licensee MDPI, Basel, Switzerland.
Source Title: Cancers
ISSN: 2072-6694
DOI: 10.3390/cancers13071538
Rights: Attribution 4.0 International
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