Evidence map›Paper›PMID 24727326›Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2014

Ganitumab (AMG 479) inhibits IGF-II-dependent ovarian cancer growth and potentiates platinum-based chemotherapy.

Pedro J Beltran, Frank J Calzone, Petia Mitchell, Young-Ah Chung, Elaina Cajulis, Gordon Moody, Brian Belmontes, Chi-Ming Li, Steven Vonderfecht, Victor E Velculescu and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed, 1 pooled it
4.3field-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

30 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.

  1. Pooled it
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  6. Insulin-like growth factor receptor signaling in physiology and disease.Signal transduction and targeted therapy · 2026
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  18. Insulin-Like Growth Factor 1 (IGF1) Pathway Member Polymorphisms Are Associated with Risk and Prognosis of Chondrosarcoma.Medical science monitor : international medical journal of experimental and clinical research · 2020
    Article
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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

14 authors at 5 institutions in 1 country.

Pedro J BeltranAuthors' Affiliations: Oncology Research Therapeutic Area, Genomics Analysis Unit, Department of Pathology, Amgen Inc., Thousand Oaks; Division of Hematology-Oncology, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California; and The Ludwig Center and the Howard Hughes Medical Institute, Kimmel Cancer Center, Johns Hopkins Medical Institutions, Baltimore, Maryland pbeltran@amgen.com.
Frank J CalzoneAuthors' Affiliations: Oncology Research Therapeutic Area, Genomics Analysis Unit, Department of Pathology, Amgen Inc., Thousand Oaks; Division of Hematology-Oncology, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California; and The Ludwig Center and the Howard Hughes Medical Institute, Kimmel Cancer Center, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Petia MitchellAuthors' Affiliations: Oncology Research Therapeutic Area, Genomics Analysis Unit, Department of Pathology, Amgen Inc., Thousand Oaks; Division of Hematology-Oncology, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California; and The Ludwig Center and the Howard Hughes Medical Institute, Kimmel Cancer Center, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Young-Ah ChungAuthors' Affiliations: Oncology Research Therapeutic Area, Genomics Analysis Unit, Department of Pathology, Amgen Inc., Thousand Oaks; Division of Hematology-Oncology, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California; and The Ludwig Center and the Howard Hughes Medical Institute, Kimmel Cancer Center, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Elaina CajulisAuthors' Affiliations: Oncology Research Therapeutic Area, Genomics Analysis Unit, Department of Pathology, Amgen Inc., Thousand Oaks; Division of Hematology-Oncology, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California; and The Ludwig Center and the Howard Hughes Medical Institute, Kimmel Cancer Center, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Gordon MoodyAuthors' Affiliations: Oncology Research Therapeutic Area, Genomics Analysis Unit, Department of Pathology, Amgen Inc., Thousand Oaks; Division of Hematology-Oncology, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California; and The Ludwig Center and the Howard Hughes Medical Institute, Kimmel Cancer Center, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Brian BelmontesAuthors' Affiliations: Oncology Research Therapeutic Area, Genomics Analysis Unit, Department of Pathology, Amgen Inc., Thousand Oaks; Division of Hematology-Oncology, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California; and The Ludwig Center and the Howard Hughes Medical Institute, Kimmel Cancer Center, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Chi-Ming LiAuthors' Affiliations: Oncology Research Therapeutic Area, Genomics Analysis Unit, Department of Pathology, Amgen Inc., Thousand Oaks; Division of Hematology-Oncology, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California; and The Ludwig Center and the Howard Hughes Medical Institute, Kimmel Cancer Center, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Steven VonderfechtAuthors' Affiliations: Oncology Research Therapeutic Area, Genomics Analysis Unit, Department of Pathology, Amgen Inc., Thousand Oaks; Division of Hematology-Oncology, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California; and The Ludwig Center and the Howard Hughes Medical Institute, Kimmel Cancer Center, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Victor E VelculescuAuthors' Affiliations: Oncology Research Therapeutic Area, Genomics Analysis Unit, Department of Pathology, Amgen Inc., Thousand Oaks; Division of Hematology-Oncology, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California; and The Ludwig Center and the Howard Hughes Medical Institute, Kimmel Cancer Center, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Guorong YangAuthors' Affiliations: Oncology Research Therapeutic Area, Genomics Analysis Unit, Department of Pathology, Amgen Inc., Thousand Oaks; Division of Hematology-Oncology, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California; and The Ludwig Center and the Howard Hughes Medical Institute, Kimmel Cancer Center, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Jingwei QiAuthors' Affiliations: Oncology Research Therapeutic Area, Genomics Analysis Unit, Department of Pathology, Amgen Inc., Thousand Oaks; Division of Hematology-Oncology, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California; and The Ludwig Center and the Howard Hughes Medical Institute, Kimmel Cancer Center, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Dennis J SlamonAuthors' Affiliations: Oncology Research Therapeutic Area, Genomics Analysis Unit, Department of Pathology, Amgen Inc., Thousand Oaks; Division of Hematology-Oncology, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California; and The Ludwig Center and the Howard Hughes Medical Institute, Kimmel Cancer Center, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Gottfried E KonecnyAuthors' Affiliations: Oncology Research Therapeutic Area, Genomics Analysis Unit, Department of Pathology, Amgen Inc., Thousand Oaks; Division of Hematology-Oncology, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California; and The Ludwig Center and the Howard Hughes Medical Institute, Kimmel Cancer Center, Johns Hopkins Medical Institutions, Baltimore, Maryland.
University of California, Los Angeles · USJohns Hopkins University · USSidney Kimmel Cancer Center · USAmgen (United States) · USHoward Hughes Medical Institute · US

Funding

Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI Rosalie Wollett · 1985 to 2026
$208.6M
Large-Scale Genetic Analyses of Human CancerR01CA121113 · NCI · JOHNS HOPKINS UNIVERSITY · PI ANAGNOSTOU, VALSAMO, VELCULESCU, VICTOR E. · 2006 to 2022
$4.3M
NCI NIH HHS P30 CA006973NCI NIH HHS R01 CA121113
6 · The paper itself

Abstract

purposeInsulin-like growth factor 1 receptor (IGF-IR) has been implicated in the pathogenesis of ovarian cancer. Ganitumab is an investigational, fully human monoclonal antibody against IGF-IR. Here, we explore the therapeutic potential of ganitumab for the treatment of ovarian cancer. EXPERIMENTAL

designThe effects of ganitumab were tested in vitro against a panel of 23 established ovarian cancer cell lines. The ability of ganitumab to inhibit IGF-I-, IGF-II-, and insulin-mediated signaling was examined in vitro and in tumor xenografts using ovarian cancer models displaying IGF-IR/PI3K/AKT pathway activation by two distinct mechanisms, PTEN loss and IGF-II overexpression. Drug interactions between ganitumab and cisplatin, carboplatin, or paclitaxel were studied in vitro and in vivo.

resultsIn vitro, growth inhibition varied significantly among individual ovarian cancer cell lines. IGF-II mRNA and phospho-IGF-IR protein expression were quantitatively correlated with response to ganitumab, and PTEN mutations conferred resistance to ganitumab. Ganitumab potently inhibited baseline and IGF-I-, IGF-II-, and insulin-induced IGF-IR and IGF-IR/insulin hybrid receptor signaling in vitro and in vivo. Synergistic and additive drug interactions were seen for ganitumab and carboplatin or paclitaxel in vitro. Furthermore, ganitumab significantly increased the efficacy of cisplatin in ovarian cancer xenograft models in vivo.

conclusionsThese observations provide a biologic rationale to test ganitumab as a single agent or in combination with carboplatin/cisplatin and paclitaxel in patients with ovarian cancer. Moreover, assessment of tumor expression of IGF-II, phospho-IGF-IR, or PTEN status may help select patients with ovarian cancer who are most likely to benefit from ganitumab. Clin Cancer Res; 20(11); 2947-58. ©2014 AACR.

Indexed as

AnimalsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic AgentsBlotting, WesternCarboplatinCell Line, TumorCell ProliferationCisplatinDrug SynergismFemaleFlow CytometryHumansInsulin-Like Growth Factor IIMiceMice, NudeAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic AgentsCarboplatinCisplatinganitumabInsulin-Like Growth Factor IIPaclitaxelPTEN PhosphohydrolaseReceptor, IGF Type 1

Identifiers

PMID24727326
PMCPMC4138720
OpenAlexW2094145539

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.