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Indoleamine Dioxygenase Inhibitors: Clinical Rationale and Current Development

  • Evolving Therapies (RM Bukowski, Section Editor)
  • Published:
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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.

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Funding

This work was supported by grants from the Canadian Cancer Society and the Liddy Shriver Sarcoma Initiative.

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Authors and Affiliations

  1. Genetic Pathology Evaluation Centre, Department of Pathology & Laboratory Medicine, University of British Columbia, 509-3660 Oak St, Vancouver, BC, V5Z 1M9, Canada

    Mayanne M. T. Zhu, Amanda R. Dancsok & Torsten O. Nielsen

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  1. Mayanne M. T. Zhu
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  2. Amanda R. Dancsok
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  3. Torsten O. Nielsen
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Correspondence to Torsten O. Nielsen.

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Mayanne M.T. Zhu declares that she has no conflict of interest.

Amanda R. Dancsok declares that she has no conflict of interest.

Torsten O. Nielsen has received research funding through a grant from Novartis; has received compensation as well as non-financial support from NanoString Technologies, Inc., for service as a consultant; has received compensation from Epizyme for service as a consultant; and has a patent (PAM50 breast cancer subtype and prognostic signature) issued, licensed to NanoString Technologies, and receives royalties, although this is not directly related to the submitted work.

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Zhu, M.M.T., Dancsok, A.R. & Nielsen, T.O. Indoleamine Dioxygenase Inhibitors: Clinical Rationale and Current Development. Curr Oncol Rep 21, 2 (2019). https://doi.org/10.1007/s11912-019-0750-1

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