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Indoleamine Dioxygenase Inhibitors : Clinical Rationale & Current Development Zhu, Mayanne; Dancsok, Amanda R.; Nielsen, Torsten

Abstract

Purpose of review: This review focuses on the recent clinical development of indolamine-2,3- dioxygenase-1 (IDO-1) inhibitors. Recent findings: IDO-1 alters tryptophan metabolism in a manner enhancing T-regulatory cell activity, but pre-clinical data show that its role in tumorigenesis is context-dependent on host and tumor interaction, highlighting some challenges in understanding the molecular oncology of this enzymatic drug target. Because results from phase I/II trials of IDO-1 inhibitor monotherapy have been disappointing, current clinical trials employ IDO-1 inhibitors in combination strategies with other immunotherapy agents or with chemotherapy +/- radiation. Combinations with anti PD-1/PD-L1 antibodies are already showing promise, and related strategies are under active evaluation. Summary: While further research is needed to elucidate the precise role of IDO-1 in tumor development, its mechanisms of action appear sufficiently distinct from other immunotherapy targets to warrant inclusion in combination immunotherapy regimens, an approach where multiple clinical trials are currently underway.

Item Metadata

Title
Indoleamine Dioxygenase Inhibitors : Clinical Rationale & Current Development
Creator
Zhu, Mayanne; Dancsok, Amanda R.; Nielsen, Torsten
Publisher
Current Oncology Reports
Date Issued
2019-01-18
Description
Purpose of review: This review focuses on the recent clinical development of indolamine-2,3- dioxygenase-1 (IDO-1) inhibitors. Recent findings: IDO-1 alters tryptophan metabolism in a manner enhancing T-regulatory cell activity, but pre-clinical data show that its role in tumorigenesis is context-dependent on host and tumor interaction, highlighting some challenges in understanding the molecular oncology of this enzymatic drug target. Because results from phase I/II trials of IDO-1 inhibitor monotherapy have been disappointing, current clinical trials employ IDO-1 inhibitors in combination strategies with other immunotherapy agents or with chemotherapy +/- radiation. Combinations with anti PD-1/PD-L1 antibodies are already showing promise, and related strategies are under active evaluation. Summary: While further research is needed to elucidate the precise role of IDO-1 in tumor development, its mechanisms of action appear sufficiently distinct from other immunotherapy targets to warrant inclusion in combination immunotherapy regimens, an approach where multiple clinical trials are currently underway.
Subject
Immune checkpoint blockade; Immuno-oncology; Combination therapy; Epacadostat; Indoximod; BMS-986205
Genre
Article; Postprint
Type
Text
Language
eng
Date Available
2021-07-12
Provider
Vancouver : University of British Columbia Library
Rights
Attribution-NonCommercial-NoDerivatives 4.0 International
DOI
10.14288/1.0400117
URI
http://hdl.handle.net/2429/78906
Affiliation
Medicine, Faculty of; Pathology and Laboratory Medicine, Department of
Citation
Zhu MMT, Dancsok AR, Nielsen TO. Indoleamine Dioxygenase Inhibitors: Clinical Rationale and Current Development. Curr Oncol Rep. 2019 Jan 18;21(1):2
Publisher DOI
10.1007/s11912-019-0750-1
Peer Review Status
Reviewed
Scholarly Level
Faculty; Graduate
Rights URI
http://creativecommons.org/licenses/by-nc-nd/4.0/
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Attribution-NonCommercial-NoDerivatives 4.0 International