Evidence map›Paper›PMID 30356039›Full record

ReviewCell death & disease2018

T-LAK cell-originated protein kinase (TOPK): an emerging target for cancer-specific therapeutics.

Katharine J Herbert, Thomas M Ashton, Remko Prevo, Giacomo Pirovano, Geoff S Higgins

Open access · goldAbstract readReview
In one paragraph

Review in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed, 2 pooled it
3.4field-weighted citation impact, top 6% 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

59 citing papers in PubMed, 2 syntheses or guidelines pooled it, 86 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Review
  4. Article
  5. Targeting the TOPK-STAT3 pathway in keratinocytes and mast cells mediates the therapeutic attenuation of Atopic dermatitis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
    Article
  6. Review
  7. Review
  8. Article
  9. TOPK Suppresses the CD8Cancer communications (London, England) · 2026
    Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article
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

5 authors at 2 institutions in 2 countries.

Katharine J HerbertCRUK/MRC Oxford Institute for Radiation Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, OX3 7DQ, UK. katharine.herbert@oncology.ox.ac.uk.ORCID http://orcid.org/0000-0001-9437-0253
Thomas M AshtonCRUK/MRC Oxford Institute for Radiation Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, OX3 7DQ, UK.
Remko PrevoCRUK/MRC Oxford Institute for Radiation Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, OX3 7DQ, UK.
Giacomo PirovanoDepartment of Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Geoff S HigginsCRUK/MRC Oxford Institute for Radiation Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, OX3 7DQ, UK.
University of Oxford · GBMemorial Sloan Kettering Cancer Center · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
Cancer Research UK 19590Medical Research Council MC_UU_00001/5NCI NIH HHS P30 CA008748
6 · The paper itself

Abstract

'Targeted' or 'biological' cancer treatments rely on differential gene expression between normal tissue and cancer, and genetic changes that render tumour cells especially sensitive to the agent being applied. Problems exist with the application of many agents as a result of damage to local tissues, tumour evolution and treatment resistance, or through systemic toxicity. Hence, there is a therapeutic need to uncover specific clinical targets which enhance the efficacy of cancer treatment whilst minimising the risk to healthy tissues. T-LAK cell-originated protein kinase (TOPK) is a MAPKK-like kinase which plays a role in cell cycle regulation and mitotic progression. As a consequence, TOPK expression is minimal in differentiated cells, although its overexpression is a pathophysiological feature of many tumours. Hence, TOPK has garnered interest as a cancer-specific biomarker and biochemical target with the potential to enhance cancer therapy whilst causing minimal harm to normal tissues. Small molecule inhibitors of TOPK have produced encouraging results as a stand-alone treatment in vitro and in vivo, and are expected to advance into clinical trials in the near future. In this review, we present the current literature pertaining to TOPK as a potential clinical target and describe the progress made in uncovering its role in tumour development. Firstly, we describe the functional role of TOPK as a pro-oncogenic kinase, followed by a discussion of its potential as a target for the treatment of cancers with high-TOPK expression. Next, we provide an overview of the current preclinical progress in TOPK inhibitor discovery and development, with respect to future adaptation for clinical use.

Indexed as

Molecular Targeted TherapyAnimalsBiomarkers, TumorCell Line, TumorDisease Models, AnimalDrug DiscoveryHumansIndolizinesMiceMitogen-Activated Protein Kinase KinasesNeoplasmsQuinolonesQuinoxalinesThiophenesTreatment OutcomeBiomarkers, TumorIndolizinesMitogen-Activated Protein Kinase KinasesN-(12-cyanoindolizino(2,3-b)quinoxalin-2-yl)thiophene-2-carboxamideOTS514PDZ-binding kinaseQuinolonesQuinoxalinesThiophenes

Identifiers

PMID30356039
PMCPMC6200809
OpenAlexW2898517569

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.