Editing Reactive oxygen species (section)

===Cancer therapy===
[[File:Open source and reduced expenditure ROS generation strategy.pdf|thumb|The scheme of fabrication process and therapeutic mechanism of thermo-responsive (MSNs@CaO2-ICG)@LA NPs for synergistic CDT/PDT with H2O2/O2 self-supply and GSH depletion]]

Both ROS-elevating and ROS-eliminating strategies have been developed with the former being predominantly used. Cancer cells with elevated ROS levels depend heavily on the antioxidant defense system. ROS-elevating drugs further increase cellular ROS stress level, either by direct ROS-generation (e.g. motexafin gadolinium, elesclomol) or by agents that abrogate the inherent antioxidant system such as SOD inhibitor (e.g. ATN-224, 2-methoxyestradiol) and GSH inhibitor (e.g. PEITC, buthionine sulfoximine (BSO)). The result is an overall increase in endogenous ROS, which when above a cellular tolerability threshold, may induce cell death.<ref>{{Cite journal |vauthors=Schumacker PT |date=September 2006 |title=Reactive oxygen species in cancer cells: live by the sword, die by the sword |journal=Cancer Cell |volume=10 |issue=3 |pages=175–176 |doi=10.1016/j.ccr.2006.08.015 |pmid=16959608 |doi-access=free}}</ref> On the other hand, normal cells appear to have, under lower basal stress and reserve, a higher capacity to cope with additional ROS-generating insults than cancer cells do.<ref>{{Cite journal |vauthors=Trachootham D, Alexandre J, Huang P |date=July 2009 |title=Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach? |journal=Nature Reviews. Drug Discovery |volume=8 |issue=7 |pages=579–591 |doi=10.1038/nrd2803 |pmid=19478820 |s2cid=20697221}}</ref> Therefore, the elevation of ROS in all cells can be used to achieve the selective killing of cancer cells.

Radiotherapy also relies on ROS toxicity to eradicate tumor cells. Radiotherapy uses X-rays, γ-rays as well as heavy particle radiation such as protons and neutrons to induce ROS-mediated cell death and mitotic failure.<ref name="pmid22117137" />

Due to the dual role of ROS, both prooxidant and antioxidant-based anticancer agents have been developed. However, modulation of ROS signaling alone seems not to be an ideal approach due to adaptation of cancer cells to ROS stress, redundant pathways for supporting cancer growth and toxicity from ROS-generating anticancer drugs. Combinations of ROS-generating drugs with pharmaceuticals that can break the redox adaptation could be a better strategy for enhancing cancer cell cytotoxicity.<ref name="pmid22117137" />

[[James Watson]]<ref>{{Cite journal |vauthors=Watson JD |date=March 2014 |title=Type 2 diabetes as a redox disease |journal=Lancet |volume=383 |issue=9919 |pages=841–843 |doi=10.1016/s0140-6736(13)62365-x |pmid=24581668 |s2cid=1076963}}</ref> and others<ref name="ReferenceA">{{Cite journal |vauthors=Molenaar RJ, van Noorden CJ |date=September 2014 |title=Type 2 diabetes and cancer as redox diseases? |journal=Lancet |volume=384 |issue=9946 |pages=853 |doi=10.1016/s0140-6736(14)61485-9 |pmid=25209484 |s2cid=28902284 |doi-access=free}}</ref> have proposed that lack of intracellular ROS due to a lack of physical exercise may contribute to the malignant progression of cancer, because spikes of ROS are needed to correctly fold proteins in the endoplasmatic reticulum and low ROS levels may thus aspecifically hamper the formation of tumor suppressor proteins.<ref name="ReferenceA" /> Since physical exercise induces temporary spikes of ROS, this may explain why physical exercise is beneficial for cancer patient prognosis.<ref>{{Cite journal |display-authors=6 |vauthors=Irwin ML, Smith AW, McTiernan A, Ballard-Barbash R, Cronin K, Gilliland FD, Baumgartner RN, Baumgartner KB, Bernstein L |date=August 2008 |title=Influence of pre- and postdiagnosis physical activity on mortality in breast cancer survivors: the health, eating, activity, and lifestyle study |journal=Journal of Clinical Oncology |volume=26 |issue=24 |pages=3958–3964 |doi=10.1200/jco.2007.15.9822 |pmc=2654316 |pmid=18711185}}</ref> Moreover, high inducers of ROS such as 2-deoxy-D-glucose and carbohydrate-based inducers of cellular stress induce cancer cell death more potently because they exploit the cancer cell's high avidity for sugars.<ref>{{Cite journal |vauthors=Ndombera FT, VanHecke GC, Nagi S, Ahn YH |date=March 2016 |title=Carbohydrate-based inducers of cellular stress for targeting cancer cells |journal=Bioorganic & Medicinal Chemistry Letters |volume=26 |issue=5 |pages=1452–1456 |doi=10.1016/j.bmcl.2016.01.063 |pmid=26832785}}</ref>
<references group="Carbohydrate-based inducers of cellular stress for targeting cancer cells Fidelis T. Ndombera, Garrett C. VanHecke, Shima Nagi, Young-Hoon Ahn"/><!--====ROS-directed cancer chemotherapeutics====
Recent research demonstrates that redox dysregulation originating from metabolic alterations and dependence on [[mitogenic]] and survival signaling through ROS represents a specific vulnerability of malignant cells that can be selectively targeted by pro- and antioxidant redox chemotherapeutics.<ref>{{Cite journal |vauthors=Wondrak GT |date=December 2009 |title=Redox-directed cancer therapeutics: molecular mechanisms and opportunities |journal=Antioxidants & Redox Signaling |volume=11 |issue=12 |pages=3013–69 |doi=10.1089/ARS.2009.2541 |pmc=2824519 |pmid=19496700}}</ref> -->