Evidence map›Paper›PMID 26364612›Full record

ArticleOncogene2016

Targeting colorectal cancer via its microenvironment by inhibiting IGF-1 receptor-insulin receptor substrate and STAT3 signaling.

E Sanchez-Lopez, E Flashner-Abramson, S Shalapour, Z Zhong, K Taniguchi, A Levitzki, M Karin

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Oncogene, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers.

0numbers the graph read from it
0cells of the map it votes in
100citing papers in PubMed
11.2field-weighted citation impact, top 1% 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

100 citing papers in PubMed, 159 citations in OpenAlex.

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  11. The role of adipogenic niche resident cells in colorectal cancer progression in relation to obesity.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2025
    Review
  12. Article
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  14. Article
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  16. Advancements in 3D In Vitro Models for Colorectal Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024
    Review
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  18. Review
  19. Article
  20. Review

40 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 3 countries.

E Sanchez-LopezLaboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, School of Medicine, University of California, San Diego, La Jolla, CA, USA.
E Flashner-AbramsonUnit of Cellular Signaling, Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.
S ShalapourLaboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, School of Medicine, University of California, San Diego, La Jolla, CA, USA.
Z ZhongLaboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, School of Medicine, University of California, San Diego, La Jolla, CA, USA.
K TaniguchiLaboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, School of Medicine, University of California, San Diego, La Jolla, CA, USA.
A LevitzkiUnit of Cellular Signaling, Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.
M KarinLaboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, School of Medicine, University of California, San Diego, La Jolla, CA, USA.
University of California, San Diego · USHebrew University of Jerusalem · ILKeio University · JP

Funding

REGULATION OF NFKB AND IKK BY PROINFLAMMATORY STIMULIR01AI043477 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KARIN, MICHAEL · 1998 to 2017
$7.4M
NF-kappaB and Mitochondrial Signals as Positive and Negative Regulators of InflammationR37AI043477 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Michael Karin · 2018 to 2026
$6.0M
Role of Inflammation in tumor promotion and progressionR01CA118165 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KARIN, MICHAEL · 2007 to 2016
$4.6M
NCI NIH HHS R01 CA118165NIAID NIH HHS R01 AI043477NIAID NIH HHS R37 AI043477
6 · The paper itself

Abstract

The tumor microenvironment (TME) exerts critical pro-tumorigenic effects through cytokines and growth factors that support cancer cell proliferation, survival, motility and invasion. Insulin-like growth factor-1 (IGF-1) and signal transducer and activator of transcription 3 (STAT3) stimulate colorectal cancer development and progression via cell autonomous and microenvironmental effects. Using a unique inhibitor, NT157, which targets both IGF-1 receptor (IGF-1R) and STAT3, we show that these pathways regulate many TME functions associated with sporadic colonic tumorigenesis in CPC-APC mice, in which cancer development is driven by loss of the Apc tumor suppressor gene. NT157 causes a substantial reduction in tumor burden by affecting cancer cells, cancer-associated fibroblasts (CAF) and myeloid cells. Decreased cancer cell proliferation and increased apoptosis were accompanied by inhibition of CAF activation and decreased inflammation. Furthermore, NT157 inhibited expression of pro-tumorigenic cytokines, chemokines and growth factors, including IL-6, IL-11 and IL-23 as well as CCL2, CCL5, CXCL7, CXCL5, ICAM1 and TGFβ; decreased cancer cell migratory activity and reduced their proliferation in the liver. NT157 represents a new class of anti-cancer drugs that affect both the malignant cell and its supportive microenvironment.

Indexed as

Adenomatous Polyposis Coli ProteinAnimalsAntineoplastic AgentsCell Line, TumorCell ProliferationColorectal NeoplasmsMacrophage ActivationMiceMice, Inbred C57BLMolecular Targeted TherapyNeoplasm MetastasisReceptor, IGF Type 1Receptor, InsulinSignal TransductionSTAT3 Transcription FactorTumor BurdenAdenomatous Polyposis Coli Proteinadenomatous polyposis coli protein, mouseAntineoplastic AgentsReceptor, IGF Type 1Receptor, InsulinSTAT3 Transcription Factor

Identifiers

PMID26364612
PMCPMC4791217
OpenAlexW2175412058

What OpenQuestion holds

Textmetadata
LicenceTDM
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.