Evidence map›Paper›PMID 31819194›Full record

ReviewBritish journal of cancer2020

The therapeutic potential of targeting tryptophan catabolism in cancer.

Christiane A Opitz, Luis F Somarribas Patterson, Soumya R Mohapatra, Dyah L Dewi, Ahmed Sadik, Michael Platten, Saskia Trump

Open access · hybridAbstract readReview
In one paragraph

Review in British journal of cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 184 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
184citing papers in PubMed, 1 pooled it
9.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

184 citing papers in PubMed, 1 synthesis or guideline pooled it, 288 citations in OpenAlex.

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124 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 2 countries.

Christiane A OpitzDKTK Brain Cancer Metabolism Group, German Cancer Research Center (DKFZ), Heidelberg, Germany. c.opitz@dkfz.de.ORCID http://orcid.org/0000-0001-5575-9821
Luis F Somarribas Patterson *DKTK Brain Cancer Metabolism Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Soumya R Mohapatra *DKTK Brain Cancer Metabolism Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Dyah L Dewi *DKTK Brain Cancer Metabolism Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Ahmed SadikDKTK Brain Cancer Metabolism Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Michael PlattenDKTK Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Saskia TrumpCharité - Universitätsmedizin Berlin and Berlin Institute of Health, Unit for Molecular Epidemiology, Berlin, Germany.
German Cancer Research Center · DEBerlin Institute of Health at Charité - Universitätsmedizin Berlin · DEUniversitas Gadjah Mada · ID

Funding

Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research) 01ZX1402EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020) No 643638EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020) No 754688
6 · The paper itself

Abstract

Based on its effects on both tumour cell intrinsic malignant properties as well as anti-tumour immune responses, tryptophan catabolism has emerged as an important metabolic regulator of cancer progression. Three enzymes, indoleamine-2,3-dioxygenase 1 and 2 (IDO1/2) and tryptophan-2,3-dioxygenase (TDO2), catalyse the first step of the degradation of the essential amino acid tryptophan (Trp) to kynurenine (Kyn). The notion of inhibiting IDO1 using small-molecule inhibitors elicited high hopes of a positive impact in the field of immuno-oncology, by restoring anti-tumour immune responses and synergising with other immunotherapies such as immune checkpoint inhibition. However, clinical trials with IDO1 inhibitors have yielded disappointing results, hence raising many questions. This review will discuss strategies to target Trp-degrading enzymes and possible down-stream consequences of their inhibition. We aim to provide comprehensive background information on Trp catabolic enzymes as targets in immuno-oncology and their current state of development. Details of the clinical trials with IDO1 inhibitors, including patient stratification, possible effects of the inhibitors themselves, effects of pre-treatments and the therapies the inhibitors were combined with, are discussed and mechanisms proposed that might have compensated for IDO1 inhibition. Finally, alternative approaches are suggested to circumvent these problems.

Indexed as

AnimalsEnzyme InhibitorsHumansImmunotherapyIndoleamine-Pyrrole 2,3,-DioxygenaseKynurenineMiceNeoplasmsTryptophanTryptophan OxygenaseEnzyme InhibitorsIDO1 protein, humanIDO2 protein, humanIndoleamine-Pyrrole 2,3,-DioxygenaseKynurenineTryptophanTryptophan Oxygenase

Identifiers

PMID31819194
PMCPMC6964670
OpenAlexW2993480792

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.