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Resistance to mTORC1 Inhibitors in Cancer Therapy: From Kinase Mutations to Intratumoral Heterogeneity of Kinase Activity
Joint Authors
Faes, Seraina
Dormond, Olivier
Demartines, Nicolas
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2017, Issue 2017 (31 Dec. 2017), pp.1-10, 10 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2017-02-09
Country of Publication
Egypt
No. of Pages
10
Main Subjects
Abstract EN
Targeting mTORC1 has been thoroughly explored in cancer therapy.
Following encouraging preclinical studies, mTORC1 inhibitors however failed to provide substantial benefits in cancer patients.
Several resistance mechanisms have been identified including mutations of mTOR and activation of alternate proliferation pathways.
Moreover, emerging evidence discloses intratumoral heterogeneity of mTORC1 activity that further contributes to a reduced anticancer efficacy of mTORC1 inhibitors.
Genetic heterogeneity as well as heterogeneous conditions of the tumor environment such as hypoxia profoundly modifies mTORC1 activity in tumors and hence influences the response of tumors to mTORC1 inhibitors.
Intriguingly, the heterogeneity of mTORC1 activity also occurs towards its substrates at the single cell level, as mutually exclusive pattern of activation of mTORC1 downstream effectors has been reported in tumors.
After briefly describing mTORC1 biology and the use of mTORC1 inhibitors in patients, this review will give an overview on concepts of resistance to mTORC1 inhibition in cancer with a particular focus on intratumoral heterogeneity of mTORC1 activity.
American Psychological Association (APA)
Faes, Seraina& Demartines, Nicolas& Dormond, Olivier. 2017. Resistance to mTORC1 Inhibitors in Cancer Therapy: From Kinase Mutations to Intratumoral Heterogeneity of Kinase Activity. Oxidative Medicine and Cellular Longevity،Vol. 2017, no. 2017, pp.1-10.
https://search.emarefa.net/detail/BIM-1193928
Modern Language Association (MLA)
Faes, Seraina…[et al.]. Resistance to mTORC1 Inhibitors in Cancer Therapy: From Kinase Mutations to Intratumoral Heterogeneity of Kinase Activity. Oxidative Medicine and Cellular Longevity No. 2017 (2017), pp.1-10.
https://search.emarefa.net/detail/BIM-1193928
American Medical Association (AMA)
Faes, Seraina& Demartines, Nicolas& Dormond, Olivier. Resistance to mTORC1 Inhibitors in Cancer Therapy: From Kinase Mutations to Intratumoral Heterogeneity of Kinase Activity. Oxidative Medicine and Cellular Longevity. 2017. Vol. 2017, no. 2017, pp.1-10.
https://search.emarefa.net/detail/BIM-1193928
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1193928