Microenvironmental and metabolic influences in tumor cell redox homeostasis
type: CreativeWork
description: Redox reactions dictate protein shape, regulate enzyme activity, and underscore cellular metabolism. When redox poise fails and cells are overcome by oxidation, cellular death soon follows. Redox biology is an especially important aspect of cancer cell biology, because oncogene-induced hyperproliferation results in pro-oxidant tumor cell phenotypes. Thus, tumor cell antioxidant systems are often inherently strained and vulnerable to further oxidative attack. Targeted therapies can be designed to kill tumor cells by pushing them beyond redox thresholds compatible with cellular life without injuring healthy cells that can more effectively dissipate oxidative stress. Radiation therapy and many chemotherapeutic drugs use this mechanism of oxidant-based cell killing to eliminate tumor cell populations. However, in clinical settings, these therapies face tumor cell resistance stemming from multifactorial changes in cellular drug and energy metabolism, environmental selective pressures, and intratumoral heterogeneity. To further advance efficacious and selective anticancer strategies, increased understanding of microenvironmental and metabolic influences in tumor cells redox homeostasis is needed. Poorly arranged and malfunctioning vasculature in the tumor microenvironment causes heterogeneous regions of hypoxia to form throughout the solid mass. Clinically, tumor hypoxia is a negative prognostic indicator for a more aggressive phenotype and is associated with treatment resistance. Metabolically, tumor hypoxia results in hypoxia inducible factor-driven gene network activation and enhanced mitochondrial production of reactive oxygen species. Given this, it is important to match laboratory in vitro studies as closely as possible to the in vivo conditions of the tumor microenvironment. However, even simple in vitro hypoxic studies are complicated by the rigors of hypoxic experimentation and, thus, most studies are conducted at hyperoxic atmospheric levels of oxygen. Engineere…
abstract: Redox reactions dictate protein shape, regulate enzyme activity, and underscore cellular metabolism. When redox poise fails and cells are overcome by oxidation, cellular death soon follows. Redox biology is an especially important aspect of cancer cell biology, because oncogene-induced hyperproliferation results in pro-oxidant tumor cell phenotypes. Thus, tumor cell antioxidant systems are often inherently strained and vulnerable to further oxidative attack. Targeted therapies can be designed to kill tumor cells by pushing them beyond redox thresholds compatible with cellular life without injuring healthy cells that can more effectively dissipate oxidative stress. Radiation therapy and many chemotherapeutic drugs use this mechanism of oxidant-based cell killing to eliminate tumor cell populations. However, in clinical settings, these therapies face tumor cell resistance stemming from multifactorial changes in cellular drug and energy metabolism, environmental selective pressures, and intratumoral heterogeneity. To further advance efficacious and selective anticancer strategies, increased understanding of microenvironmental and metabolic influences in tumor cells redox homeostasis is needed. Poorly arranged and malfunctioning vasculature in the tumor microenvironment causes heterogeneous regions of hypoxia to form throughout the solid mass. Clinically, tumor hypoxia is a negative prognostic indicator for a more aggressive phenotype and is associated with treatment resistance. Metabolically, tumor hypoxia results in hypoxia inducible factor-driven gene network activation and enhanced mitochondrial production of reactive oxygen species. Given this, it is important to match laboratory in vitro studies as closely as possible to the in vivo conditions of the tumor microenvironment. However, even simple in vitro hypoxic studies are complicated by the rigors of hypoxic experimentation and, thus, most studies are conducted at hyperoxic atmospheric levels of oxygen. Engineere…
author: Leslie, Matthew Thomas
language: en
keywords: Cancer, RAS Oncogene, Metabolism, Glutaminolysis, Glutamine, Alpha-ketoglutarate, Glutathione, GSH, Redox, Reactive Oxygen Species, Hypoxia, Microfluidics, roGFP2 biosensor
date published: 2018-09-04T20:33:44Z
date modified: 2026-07-22T22:24:38Z
provider: University of Illinois - Urbana-Champaign
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Illinois at Urbana-Champaign

PropertyValue
property ID: Handle
value: http://hdl.handle.net/2142/101106