Evidence map›Paper›PMID 32481658›Full record

ArticleCancers2020

Anti-EGFR Therapy Induces EGF Secretion by Cancer-Associated Fibroblasts to Confer Colorectal Cancer Chemoresistance.

Colleen M Garvey, Roy Lau, Alyssa Sanchez, Ren X Sun, Emma J Fong, Michael E Doche, Oscar Chen, Anthony Jusuf, Heinz-Josef Lenz, Brent Larson and 1 more

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

Article in Cancers, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed
3.8field-weighted citation impact, top 5% 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

51 citing papers in PubMed, 83 citations in OpenAlex.

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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

11 authors at 2 institutions in 1 country.

Colleen M GarveyLawrence J. Ellison Institute for Transformative Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Roy LauLawrence J. Ellison Institute for Transformative Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Alyssa SanchezLawrence J. Ellison Institute for Transformative Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Ren X SunLawrence J. Ellison Institute for Transformative Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Emma J FongLawrence J. Ellison Institute for Transformative Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Michael E DocheLawrence J. Ellison Institute for Transformative Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Oscar ChenLawrence J. Ellison Institute for Transformative Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Anthony JusufLawrence J. Ellison Institute for Transformative Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Heinz-Josef LenzDivision of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Brent LarsonDepartment of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Shannon M MumenthalerLawrence J. Ellison Institute for Transformative Medicine, University of Southern California, Los Angeles, CA 90033, USA.ORCID 0000-0003-2687-3769
University of Southern California · USCedars-Sinai Medical Center · US

Funding

USC/NORRIS COMPREHENSIVE CANCER CENTER (CORE) SUPPORTP30CA014089 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Fumito Ito · 1985 to 2026
$181.4M
TRANS-NETWORK PROJECTSU54CA143907 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI NOLAN, GARRY P · 2009 to 2013
$15.2M
NCI NIH HHS P30 CA014089NCI NIH HHS P30CA014089NCI NIH HHS U54 CA143907NCI NIH HHS U54CA143907
6 · The paper itself

Abstract

Targeted agents have improved the efficacy of chemotherapy for cancer patients, however, there remains a lack of understanding of how these therapies affect the unsuspecting bystanders of the stromal microenvironment. Cetuximab, a monoclonal antibody therapy targeting the epidermal growth factor receptor (EGFR), is given in combination with chemotherapy as the standard of care for a subset of metastatic colorectal cancer patients. The overall response to this treatment is underwhelming and, while genetic mutations that confer resistance have been identified, it is still not known why this drug is ineffective for some patients. We discovered that cancer-associated fibroblasts (CAFs), a major cellular subset of the tumor stroma, can provide a source of cancer cell resistance. Specifically, we observed that upon treatment with cetuximab, CAFs increased their secretion of EGF, which was sufficient to render neighboring cancer cells resistant to cetuximab treatment through sustained mitogen-activated protein kinases (MAPK) signaling. Furthermore, we show the cetuximab-induced EGF secretion to be specific to CAFs and not to cancer cells or normal fibroblasts. Altogether, this work emphasizes the importance of the tumor microenvironment and considering the potential unintended consequences of therapeutically targeting cancer-driving proteins on non-tumorigenic cell types.

Indexed as

cancer-associated fibroblastscetuximabcolorectal cancerdrug-resistanceepidermal growth factortumor microenvironment

Identifiers

PMID32481658
PMCPMC7352975
OpenAlexW3030459744

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.