Evidence map›Paper›PMID 28159572›Full record

ArticleEBioMedicine2017

FASN Inhibition and Taxane Treatment Combine to Enhance Anti-tumor Efficacy in Diverse Xenograft Tumor Models through Disruption of Tubulin Palmitoylation and Microtubule Organization and FASN Inhibition-Mediated Effects on Oncogenic Signaling and Gene Expression.

Timothy S Heuer, Richard Ventura, Kasia Mordec, Julie Lai, Marina Fridlib, Douglas Buckley, George Kemble

Open access · goldAbstract read
In one paragraph

Article in EBioMedicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.

0numbers the graph read from it
0cells of the map it votes in
75citing papers in PubMed
3.3field-weighted citation impact, top 8% 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

75 citing papers in PubMed, 130 citations in OpenAlex.

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  15. Reprogramming of fatty acid metabolism in thyroid cancer: Potential targets and mechanisms.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2025
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  19. S-acylation of CaChronic diseases and translational medicine · 2024
    Review
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15 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 1 institution in 1 country.

Timothy S Heuer3-V Biosciences, Menlo Park, CA, USA. Electronic address: tim@celldesignlabs.com.
Richard Ventura3-V Biosciences, Menlo Park, CA, USA.
Kasia Mordec3-V Biosciences, Menlo Park, CA, USA.
Julie Lai3-V Biosciences, Menlo Park, CA, USA.
Marina Fridlib3-V Biosciences, Menlo Park, CA, USA.
Douglas Buckley3-V Biosciences, Menlo Park, CA, USA.
George Kemble3-V Biosciences, Menlo Park, CA, USA.
Pacific Biosciences (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Palmitate, the enzymatic product of FASN, and palmitate-derived lipids support cell metabolism, membrane architecture, protein localization, and intracellular signaling. Tubulins are among many proteins that are modified post-translationally by acylation with palmitate. We show that FASN inhibition with TVB-3166 or TVB-3664 significantly reduces tubulin palmitoylation and mRNA expression. Disrupted microtubule organization in tumor cells is an additional consequence of FASN inhibition. FASN inhibition combined with taxane treatment enhances inhibition of in vitro tumor cell growth compared to treatment with either agent alone. In lung, ovarian, prostate, and pancreatic tumor xenograft studies, FASN inhibition and paclitaxel or docetaxel combine to inhibit xenograft tumor growth with significantly enhanced anti-tumor activity. Tumor regression was observed in 3 of 6 tumor xenograft models. FASN inhibition does not affect cellular taxane concentration in vitro. Our data suggest a mechanism of enhanced anti-tumor activity of the FASN and taxane drug combination that includes inhibition of tubulin palmitoylation and disruption of microtubule organization in tumor cells, as well as a sensitization of tumor cells to FASN inhibition-mediated effects that include gene expression changes and inhibition of β-catenin. Together, the results strongly support investigation of combined FASN inhibition and taxane treatment as a therapy for a variety of human cancers.

Indexed as

A549 CellsAnimalsAntineoplastic AgentsAzetidinesbeta CateninBlotting, WesternBridged-Ring CompoundsCarcinogenesisCell LineCell Line, TumorEnzyme InhibitorsFatty Acid Synthase, Type IFemaleGene Expression Regulation, NeoplasticHumansLipoylation4-(1-(5-(3,4-dimethyl-1H-pyrazol-5-yl)-2,4-dimethylbenzoyl)azetidin-3-yl)benzonitrileAntineoplastic AgentsAzetidinesbeta CateninBridged-Ring CompoundsEnzyme InhibitorsFASN protein, humanFatty Acid Synthase, Type INitrilesPyrazolestaxaneTaxoidsTubulinTVB-3664Docetaxel, combinationFatty acid synthaseInhibitorPaclitaxelPalmitoylation

Identifiers

PMID28159572
PMCPMC5474427
OpenAlexW2567412474

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.