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Overcoming Drug Resistance Through Elevation of ROS in Cancer

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Molecular Mechanisms of Tumor Cell Resistance to Chemotherapy

Part of the book series: Resistance to Targeted Anti-Cancer Therapeutics ((RTACT,volume 1))

Abstract

Drug resistance is the most devastating problem in treating cancer and drug-resistant cells are harder to kill with the same drug. The mechanism of drug resistance is believed to differ in various cancers for different anticancer drugs. Most of the anticancer agents induce the generation of Reactive Oxygen Species (ROS) to kill cancer cells by apoptosis. However, prolonged treatment with the same drug reduces the ROS level and this reduced ROS level causes drug-sensitive cancer cells to become drug-resistant. Exogenous ROS in conjunction with the same drug resensitizes these drug-resistant cells. Thus, the apoptosis of cancer cells by inducing ROS generation or drug resistance by lack of ROS could be the principle mechanisms of drug sensitivity or drug resistance in various cancer cells. The genetic mechanism of ROS-induced drug sensitivity and ROS depletion leading to drug resistance in various cancer cells with most of the anticancer drugs could involve ‘common molecular pathways’. Understanding the molecular mechanism of ROS generation and maintenance could identify distinct targets for subsequent manipulation to elevate ROS levels in cancer cells. Thus, a ‘combinational chemotherapy’ could be designed using an anticancer drug while maintaining an elevated level of ROS in the cell during the drug treatment for developing a successful chemotherapy.

An erratum to this chapter is available at 10.1007/978-1-4614-7070-0_13

An erratum to this chapter can be found at http://dx.doi.org/10.1007/978-1-4614-7070-0_13

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Abbreviations

ABCB1:

ATP-binding cassette sub-family B member 1

APEX1:

APEX nuclease (multifunctional DNA repair enzyme) 1

CASPs:

Caspases

CAT:

Catalase

CDDO-ME:

C-28 methyl ester derivative methyl-2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oate

ERK1/2:

Extracellular-signal-regulated kinases

IPA:

Ingenuity Pathway Analysis

GST:

Glutathione-S-transferase

HIF 2-alpha:

Hypoxia-inducible factor 2, alpha subunit

hTERT:

Human telomerase reverse transcriptase

JUN:

Jun proto-oncogene

KEAP1:

Kelch-like ECH-associated protein 1

MAPK8:

Mitogen-activated protein kinase 8

MCTS:

Multi-cellular tumor spheroids

MDR1:

Multi drug resistance protein 1

NFE2L2:

Nuclear factor (erythroid-derived 2)-like 2

NF-κB:

Nuclear factor kappa-light-chain-enhancer of activated B cells

PEITC:

Phynyl isothiocyanate

ROS:

Reactive Oxygen Species

SOD:

Superoxide dismutase

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Acknowledgements

I thank Ms B. Mikkola for critically reading this manuscript.

Conflicts of Interest

No potential conflicts of interest were disclosed.

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Authors and Affiliations

  1. Department of Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma city, OK, 73104, USA

    Amit K. Maiti

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Correspondence to Amit K. Maiti .

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  1. Dept. Microbiology, Immunology &, Molecular Genetics, University of California, Los Angeles, Charles E. Young Dr. E. 609, Los Angeles, 90095, California, USA

    Benjamin Bonavida

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Maiti, A.K. (2013). Overcoming Drug Resistance Through Elevation of ROS in Cancer. In: Bonavida, B. (eds) Molecular Mechanisms of Tumor Cell Resistance to Chemotherapy. Resistance to Targeted Anti-Cancer Therapeutics, vol 1. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-7070-0_7

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