TY - JOUR
T1 - The kynurenine pathway presents multi-faceted metabolic vulnerabilities in cancer
AU - León-Letelier, Ricardo A.
AU - Dou, Rongzhang
AU - Vykoukal, Jody
AU - Sater, Ali Hussein Abdel
AU - Ostrin, Edwin
AU - Hanash, Samir
AU - Fahrmann, Johannes F.
N1 - Publisher Copyright:
Copyright © 2023 León-Letelier, Dou, Vykoukal, Sater, Ostrin, Hanash and Fahrmann.
PY - 2023
Y1 - 2023
N2 - The kynurenine pathway (KP) and associated catabolites play key roles in promoting tumor progression and modulating the host anti-tumor immune response. To date, considerable focus has been on the role of indoleamine 2,3-dioxygenase 1 (IDO1) and its catabolite, kynurenine (Kyn). However, increasing evidence has demonstrated that downstream KP enzymes and their associated metabolite products can also elicit tumor-microenvironment immune suppression. These advancements in our understanding of the tumor promotive role of the KP have led to the conception of novel therapeutic strategies to target the KP pathway for anti-cancer effects and reversal of immune escape. This review aims to 1) highlight the known biological functions of key enzymes in the KP, and 2) provide a comprehensive overview of existing and emerging therapies aimed at targeting discrete enzymes in the KP for anti-cancer treatment.
AB - The kynurenine pathway (KP) and associated catabolites play key roles in promoting tumor progression and modulating the host anti-tumor immune response. To date, considerable focus has been on the role of indoleamine 2,3-dioxygenase 1 (IDO1) and its catabolite, kynurenine (Kyn). However, increasing evidence has demonstrated that downstream KP enzymes and their associated metabolite products can also elicit tumor-microenvironment immune suppression. These advancements in our understanding of the tumor promotive role of the KP have led to the conception of novel therapeutic strategies to target the KP pathway for anti-cancer effects and reversal of immune escape. This review aims to 1) highlight the known biological functions of key enzymes in the KP, and 2) provide a comprehensive overview of existing and emerging therapies aimed at targeting discrete enzymes in the KP for anti-cancer treatment.
KW - cancer
KW - immune evasion
KW - kynurenine pathway (KP)
KW - metabolism
KW - therapeutics
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U2 - 10.3389/fonc.2023.1256769
DO - 10.3389/fonc.2023.1256769
M3 - Review article
C2 - 37876966
AN - SCOPUS:85174600290
SN - 2234-943X
VL - 13
JO - Frontiers in Oncology
JF - Frontiers in Oncology
M1 - 1256769
ER -