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Role of Kynurenine Pathway in Cancer Biology

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Targeting the Broadly Pathogenic Kynurenine Pathway

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Abstract

The kynurenine pathway for tryptophan catabolism is responsible for the production of the essential cofactor NAD+, but many of the pathway catabolites play roles in many different disease states. The involvement of the kynurenine pathway enzymes and catabolites in cancer occurs via both immune and nonimmune mechanisms. In this chapter, the consequences of the immune response to developing tumors will be summarized, and the role played by indoleamine 2,3-dioxygenase in enabling tumor immune escape via tryptophan depletion will be outlined. In addition, the role played by other enzymes, such as tryptophan 2,3-dioxygenase—which modulates the immune response by producing kynurenine—is described. Further to this, the involvement of downstream enzymes and catabolites of the pathway in tumor development is discussed.

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Abbreviations

KP:

Kynurenine pathway

IDO:

Indoleamine 2,3-dioxygenase

IDO2:

Indoleamine 2,3-dioxygenase-2

TDO:

Tryptophan 2,3-dioxygenase

NMDA:

N-methyl-D-aspartate

TRP:

L-tryptophan

KYN:

Kynurenine

KYNA:

Kynurenic acid

3-HK:

3-Hydroxykynurenine

AA:

Anthranilic acid

3-HA:

3-Hydroxyanthranilic acid

PIC:

Picolinic acid

QUIN:

Quinolinic acid

NAD+ :

Nicotinamide adenine dinucleotide

IFN:

Interferon

IL:

Interleukin

TNF:

Tumor necrosis factor

APC:

Antigen-presenting cell

DC:

Dendritic cell

AHR:

Aryl hydrocarbon receptor

ACMSD:

Aminocarboxymuconate semialdehyde decarboxylase

1-MT:

1-Methyl-tryptophan

LPS:

Lipopolysaccharide

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  1. EastChem School of Chemistry, University of Edinburgh, Joseph Black Building, David Brewster Road, Edinburgh, EH9 3FJ, UK

    Christopher G. Mowat

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  1. Chairman, Department of Neurosurgery, Wayne State University, Detroit, Michigan, USA

    Sandeep Mittal

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Mowat, C.G. (2015). Role of Kynurenine Pathway in Cancer Biology. In: Mittal, S. (eds) Targeting the Broadly Pathogenic Kynurenine Pathway. Springer, Cham. https://doi.org/10.1007/978-3-319-11870-3_21

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