Evidence map›Paper›PMID 25123819›Full record

ReviewCancer treatment reviews2014

Can we unlock the potential of IGF-1R inhibition in cancer therapy?

Helen King, Tamara Aleksic, Paul Haluska, Valentine M Macaulay

Abstract readReview
In one paragraph

Review in Cancer treatment reviews, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.

0numbers the graph read from it
0cells of the map it votes in
87citing 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

87 citing papers in PubMed.

  1. Trial
  2. Insulin-like growth factor receptor signaling in physiology and disease.Signal transduction and targeted therapy · 2026
    Review
  3. Article
  4. Review
  5. Article
  6. Structural Models for a Series of Allosteric Inhibitors of IGF1R Kinase.International journal of molecular sciences · 2024
    Article
  7. Structural Models for a Series of Allosteric Inhibitors of IGF1R Kinase.bioRxiv : the preprint server for biology · 2024
    Article
  8. Article
  9. IGF-1R targeting in cancer - does sub-cellular localization matter?Journal of experimental & clinical cancer research : CR · 2023
    Review
  10. Article
  11. Article
  12. Article
  13. Review
  14. Review
  15. Review
  16. Article
  17. Review
  18. Review
  19. Article
  20. Review

27 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

4 authors.

Helen KingSt Catherine's College, University of Oxford, Manor Road, Oxford OX1 3UJ, UK. Electronic address: helen.king@stcatz.ox.ac.uk.
Tamara AleksicDepartment of Oncology Laboratories, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DS, UK. Electronic address: taleksic13@googlemail.com.
Paul HaluskaDivision of Medical Oncology, Mayo Clinic College of Medicine, 200 First St. SW, Rochester, MN 55905, USA. Electronic address: Haluska.Paul@mayo.edu.
Valentine M MacaulayDepartment of Oncology Laboratories, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DS, UK; Oxford Cancer Centre, Churchill Hospital, Oxford OX3 7LE, UK. Electronic address: valentine.macaulay@oncology.ox.ac.uk.

Funding

The Role of CHFR in Tumorigenesis and Paclitaxel-Sensitivity in Breast CancerP50CA116201 · NCI · MAYO CLINIC ROCHESTER · PI Fergus Joseph Couch · 2005 to 2026
$49.9M
Use of microfluidic tumor cultures to enable clinical trials of therapies for ovarian cancerP50CA136393 · NCI · MAYO CLINIC ROCHESTER · PI ELLEN L. GOODE · 2009 to 2026
$37.0M
Cancer Research UKNCI NIH HHS CA116201NCI NIH HHS CA136393NCI NIH HHS P50 CA116201NCI NIH HHS P50 CA136393
6 · The paper itself

Abstract

IGF-1R inhibitors arrived in the clinic accompanied by optimism based on preclinical activity of IGF-1R targeting, and recognition that low IGF bioactivity protects from cancer. This was tempered by concerns about toxicity to normal tissue IGF-1R and cross-reactivity with insulin receptor (InsR). In fact, toxicity is not a show-stopper; the key issue is efficacy. While IGF-1R inhibition induces responses as monotherapy in sarcomas and with chemotherapy or targeted agents in common cancers, negative Phase 2/3 trials in unselected patients prompted the cessation of several Pharma programs. Here, we review completed and on-going trials of IGF-1R antibodies, kinase inhibitors and ligand antibodies. We assess candidate biomarkers for patient selection, highlighting the potential predictive value of circulating IGFs/IGFBPs, the need for standardized assays for IGF-1R, and preclinical evidence that variant InsRs mediate resistance to IGF-1R antibodies. We review hypothesis-led and unbiased approaches to evaluate IGF-1R inhibitors with other agents, and stress the need to consider sequencing with chemotherapy. The last few years were a tough time for IGF-1R therapeutics, but also brought progress in understanding IGF biology. Even failed studies include patients who derived benefit; they should be investigated to identify features distinguishing the tumors and host environment of responders from non-responders. We emphasize the importance of incorporating biospecimen collection into trial design, and wording patient consents to allow post hoc analysis of trial material as new data become available. Such information represents the key to unlocking the potential of this approach, to inform the next generation of trials of IGF signalling inhibitors.

Indexed as

Antibodies, MonoclonalAntineoplastic AgentsBiomarkers, TumorClinical Trials as TopicHumansMolecular Targeted TherapyNeoplasmsPredictive Value of TestsProtein Kinase InhibitorsReceptor, IGF Type 1Antibodies, MonoclonalAntineoplastic AgentsBiomarkers, TumorProtein Kinase InhibitorsReceptor, IGF Type 1IGFIGF-1R cancer therapyPredictive biomarkerTherapeutic antibodyType 1 IGF receptorTyrosine kinase inhibitor

Identifiers

PMID25123819
PMCPMC4196677

What OpenQuestion holds

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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.