Evidence map›Paper›PMID 26574568›Full record

ArticleEndocrine connections2016

Destabilizing RET in targeted treatment of thyroid cancers.

M L Gild, M Bullock, C K Pon, B G Robinson, R J Clifton-Bligh

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Endocrine connections, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.1field-weighted citation impact, top 20% 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

5 citing papers in PubMed, 7 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Review
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 1 country.

M L GildCancer Genetics LaboratoryKolling Institute of Medical Research, Sydney, New South Wales, AustraliaDepartment of EndocrinologyRoyal North Shore Hospital, The University of Sydney, Sydney, New South Wales 2065, Australia.
M BullockCancer Genetics LaboratoryKolling Institute of Medical Research, Sydney, New South Wales, AustraliaDepartment of EndocrinologyRoyal North Shore Hospital, The University of Sydney, Sydney, New South Wales 2065, Australia.
C K PonCancer Genetics LaboratoryKolling Institute of Medical Research, Sydney, New South Wales, AustraliaDepartment of EndocrinologyRoyal North Shore Hospital, The University of Sydney, Sydney, New South Wales 2065, Australia.
B G RobinsonCancer Genetics LaboratoryKolling Institute of Medical Research, Sydney, New South Wales, AustraliaDepartment of EndocrinologyRoyal North Shore Hospital, The University of Sydney, Sydney, New South Wales 2065, Australia Cancer Genetics LaboratoryKolling Institute of Medical Research, Sydney, New South Wales, AustraliaDepartment of EndocrinologyRoyal North Shore Hospital, The University of Sydney, Sydney, New South Wales 2065, Australia.
R J Clifton-BlighCancer Genetics LaboratoryKolling Institute of Medical Research, Sydney, New South Wales, AustraliaDepartment of EndocrinologyRoyal North Shore Hospital, The University of Sydney, Sydney, New South Wales 2065, Australia Cancer Genetics LaboratoryKolling Institute of Medical Research, Sydney, New South Wales, AustraliaDepartment of EndocrinologyRoyal North Shore Hospital, The University of Sydney, Sydney, New South Wales 2065, Australia jclifton@med.usyd.edu.au.
University of Sydney · AURoyal North Shore Hospital · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Metastatic differentiated thyroid cancers (DTC) are resistant to traditional chemotherapy. Kinase inhibitors have shown promise in patients with progressive DTC, but dose-limiting toxicity is commonplace. HSP90 regulates protein degradation of several growth-mediating kinases such as RET, and we hypothesized that HSP90 inhibitor (AUY922) could inhibit RET-mediated medullary thyroid cancer (MTC) as well as papillary thyroid cancer (PTC) cell growth and also radioactive iodine uptake by PTC cells. Studies utilized MTC cell lines TT (C634W) and MZ-CRC-1 (M918T) and the PTC cell line TPC-1 (RET/PTC1). Cell viability was assessed with MTS assays and apoptosis by flow cytometry. Signaling target expression was determined by western blot and radioiodine uptake measured with a gamma counter. Prolonged treatment of both MTC cell lines with AUY922 simultaneously inhibited both MAPK and mTOR pathways and significantly induced apoptosis (58.7 and 78.7% reduction in MZ-CRC-1 and TT live cells respectively, following 1 μM AUY922; P<0.02). Similarly in the PTC cell line, growth and signaling targets were inhibited, and also a 2.84-fold increase in radioiodine uptake was observed following AUY922 administration (P=0.015). AUY922 demonstrates in vitro activity against MTC and PTC cell lines. We observed a potent dose-dependent increase in apoptosis in MTC cell lines following drug administration confirming its anti-tumorigenic effects. Western blots confirm inhibition of pro-survival proteins including AKT suggesting this as the mechanism of cell death. In a functional study, we observed an increase in radioiodine uptake in the PTC cell line following AUY922 treatment. We believe HSP90 inhibition could be a viable alternative for treatment of RET-driven chemo-resistant thyroid cancers.

Indexed as

AUY922HSP90MAPKmTORRETthyroid cancer

Identifiers

PMID26574568
PMCPMC4674629
OpenAlexW2191454906

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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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.