Journal
CURRENT ONCOLOGY REPORTS
Volume 21, Issue 1, Pages -Publisher
SPRINGER
DOI: 10.1007/s11912-019-0750-1
Keywords
Immune checkpoint blockade; Immuno-oncology; Combination therapy; Epacadostat; Indoximod; BMS-986205
Categories
Funding
- Canadian Cancer Society
- Liddy Shriver Sarcoma Initiative
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Purpose of ReviewThis review focuses on the recent clinical development of indolamine-2,3-dioxygenase-1 (IDO-1) inhibitors.Recent FindingsIDO-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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