gRASping the redox lever to modulate cancer cell fate signaling

RAS proteins are critical regulators of signaling networks controlling diverse cellular functions such as cell proliferation and survival and its mutation are among the most powerful oncogenic drivers in human cancers. Despite intense efforts, direct RAS-targeting strategies remain elusive due to it...

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Main Authors: Foo, C., Pervaiz, Shazib
Format: Journal Article
Published: Elsevier BV 2019
Online Access:http://hdl.handle.net/20.500.11937/74805
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author Foo, C.
Pervaiz, Shazib
author_facet Foo, C.
Pervaiz, Shazib
author_sort Foo, C.
building Curtin Institutional Repository
collection Online Access
description RAS proteins are critical regulators of signaling networks controlling diverse cellular functions such as cell proliferation and survival and its mutation are among the most powerful oncogenic drivers in human cancers. Despite intense efforts, direct RAS-targeting strategies remain elusive due to its “undruggable” nature. To that end, bulk of the research efforts has been directed towards targeting upstream and/or downstream of RAS signaling. However, the therapeutic efficacies of these treatments are limited in the long run due to the acquired drug resistance in RAS-driven cancers. Interestingly, recent studies have uncovered a potential role of RAS in redox-regulation as well as the interplay between ROS and RAS-associated signaling networks during process of cancer initiation and progression. More specifically, these studies provide ample evidence to implicate RAS as a redox-rheostat, manipulating ROS levels to provide a redox-milieu conducive for carcinogenesis. Importantly, the understanding of RAS-ROS interplay could provide us with novel targetable vulnerabilities for designing therapeutic strategies. In this review, we provide a brief summary of the advances in the field to illustrate the dual role of RAS in redox-regulation and its implications in RAS signaling outcomes and also emerging redox-based strategies to target RAS-driven cancers.
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spelling curtin-20.500.11937-748052019-05-10T02:23:23Z gRASping the redox lever to modulate cancer cell fate signaling Foo, C. Pervaiz, Shazib RAS proteins are critical regulators of signaling networks controlling diverse cellular functions such as cell proliferation and survival and its mutation are among the most powerful oncogenic drivers in human cancers. Despite intense efforts, direct RAS-targeting strategies remain elusive due to its “undruggable” nature. To that end, bulk of the research efforts has been directed towards targeting upstream and/or downstream of RAS signaling. However, the therapeutic efficacies of these treatments are limited in the long run due to the acquired drug resistance in RAS-driven cancers. Interestingly, recent studies have uncovered a potential role of RAS in redox-regulation as well as the interplay between ROS and RAS-associated signaling networks during process of cancer initiation and progression. More specifically, these studies provide ample evidence to implicate RAS as a redox-rheostat, manipulating ROS levels to provide a redox-milieu conducive for carcinogenesis. Importantly, the understanding of RAS-ROS interplay could provide us with novel targetable vulnerabilities for designing therapeutic strategies. In this review, we provide a brief summary of the advances in the field to illustrate the dual role of RAS in redox-regulation and its implications in RAS signaling outcomes and also emerging redox-based strategies to target RAS-driven cancers. 2019 Journal Article http://hdl.handle.net/20.500.11937/74805 10.1016/j.redox.2018.101094 http://creativecommons.org/licenses/by-nc-nd/4.0/ Elsevier BV fulltext
spellingShingle Foo, C.
Pervaiz, Shazib
gRASping the redox lever to modulate cancer cell fate signaling
title gRASping the redox lever to modulate cancer cell fate signaling
title_full gRASping the redox lever to modulate cancer cell fate signaling
title_fullStr gRASping the redox lever to modulate cancer cell fate signaling
title_full_unstemmed gRASping the redox lever to modulate cancer cell fate signaling
title_short gRASping the redox lever to modulate cancer cell fate signaling
title_sort grasping the redox lever to modulate cancer cell fate signaling
url http://hdl.handle.net/20.500.11937/74805