Evidence map›Paper›PMID 34535764›Full record

ArticleCell death and differentiation2022

Potent pro-apoptotic combination therapy is highly effective in a broad range of cancers.

Antonella Montinaro, Itziar Areso Zubiaur, Julia Saggau, Anna-Laura Kretz, Rute M M Ferreira, Omar Hassan, Ella Kitzig, Ines Müller, Mona A El-Bahrawy, Silvia von Karstedt and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death and differentiation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
–field-weighted citation impact
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

15 citing papers in PubMed.

  1. Topotecan Synergizes with SP141 in the Management of Uveal Melanoma.bioRxiv : the preprint server for biology · 2026
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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

14 authors.

Antonella Montinaro *Centre for Cell Death, Cancer, and Inflammation (CCCI), UCL Cancer Institute, University College London, 72 Huntley Street, London, WC1E 6DD, UK.
Itziar Areso Zubiaur *Centre for Cell Death, Cancer, and Inflammation (CCCI), UCL Cancer Institute, University College London, 72 Huntley Street, London, WC1E 6DD, UK.
Julia SaggauCECAD Cluster of Excellence, University of Cologne, 50931, Cologne, Germany.
Anna-Laura KretzDepartment of General and Visceral Surgery, Ulm University Hospital, Albert-Einstein-Allee 23, 89081, Ulm, Germany.
Rute M M FerreiraCentre for Cell Death, Cancer, and Inflammation (CCCI), UCL Cancer Institute, University College London, 72 Huntley Street, London, WC1E 6DD, UK.
Omar HassanCECAD Cluster of Excellence, University of Cologne, 50931, Cologne, Germany.
Ella KitzigDepartment of General and Visceral Surgery, Ulm University Hospital, Albert-Einstein-Allee 23, 89081, Ulm, Germany.
Ines MüllerExperimental Dermatology, Department of Dermatology, Technical University Dresden, Dresden, Germany.
Mona A El-BahrawyDepartment of Histopathology, Imperial College London, London, W12 0NN, UK.
Silvia von KarstedtCentre for Cell Death, Cancer, and Inflammation (CCCI), UCL Cancer Institute, University College London, 72 Huntley Street, London, WC1E 6DD, UK.
Dagmar KulmsExperimental Dermatology, Department of Dermatology, Technical University Dresden, Dresden, Germany.ORCID http://orcid.org/0000-0001-6874-0548
Gianmaria LiccardiCenter for Biochemistry, Medical Faculty, Joseph-Stelzmann-Str. 52, University of Cologne, 50931, Cologne, Germany.
Johannes LemkeDepartment of General and Visceral Surgery, Ulm University Hospital, Albert-Einstein-Allee 23, 89081, Ulm, Germany.
Henning WalczakCentre for Cell Death, Cancer, and Inflammation (CCCI), UCL Cancer Institute, University College London, 72 Huntley Street, London, WC1E 6DD, UK. h.walczak@ucl.ac.uk.ORCID http://orcid.org/0000-0002-6312-4591

Funding

Cancer Research UK 27323Cancer Research UK 515818Cancer Research UK A27323Medical Research Council MR/S00811X/1Wellcome Trust 214342Wellcome Trust 214342/Z/18/Z
6 · The paper itself

Abstract

Primary or acquired therapy resistance is a major obstacle to the effective treatment of cancer. Resistance to apoptosis has long been thought to contribute to therapy resistance. We show here that recombinant TRAIL and CDK9 inhibition cooperate in killing cells derived from a broad range of cancers, importantly without inducing detectable adverse events. Remarkably, the combination of TRAIL with CDK9 inhibition was also highly effective on cancers resistant to both, standard-of-care chemotherapy and various targeted therapeutic approaches. Dynamic BH3 profiling revealed that, mechanistically, combining TRAIL with CDK9 inhibition induced a drastic increase in the mitochondrial priming of cancer cells. Intriguingly, this increase occurred irrespective of whether the cancer cells were sensitive or resistant to chemo- or targeted therapy. We conclude that this pro-apoptotic combination therapy has the potential to serve as a highly effective new treatment option for a variety of different cancers. Notably, this includes cancers that are resistant to currently available treatment modalities.

Indexed as

Antineoplastic AgentsNeoplasmsApoptosisCell Line, TumorMitochondriaTNF-Related Apoptosis-Inducing LigandAntineoplastic AgentsTNF-Related Apoptosis-Inducing Ligand

Identifiers

PMID34535764
PMCPMC8901660

What Socratic 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 Socratic graph.