Evidence map›Paper›PMID 30914635›Full record

ArticleNature communications2019

Aberrant FGFR signaling mediates resistance to CDK4/6 inhibitors in ER+ breast cancer.

Luigi Formisano, Yao Lu, Alberto Servetto, Ariella B Hanker, Valerie M Jansen, Joshua A Bauer, Dhivya R Sudhan, Angel L Guerrero-Zotano, Sarah Croessmann, Yan Guo and 21 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 255 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
255citing papers in PubMed, 1 pooled it
39.8field-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

255 citing papers in PubMed, 1 synthesis or guideline pooled it, 407 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Trial
  4. Trial
  5. Trial
  6. CCNE1 and PLK1 Mediate Resistance to Palbociclib in HR+/HER2- Metastatic Breast Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023
    Trial
  7. Trial
  8. Trial
  9. Trial
  10. Correlative Biomarker Analysis of Intrinsic Subtypes and Efficacy Across the MONALEESA Phase III Studies.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2021
    Trial
  11. Trial
  12. Article
  13. Review
  14. Article
  15. Article
  16. Cancers · 2026
    Review
  17. Article
  18. Review
  19. Article
  20. Article

195 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

31 authors at 9 institutions in 1 country.

Luigi FormisanoDepartments of Medicine, Vanderbilt University Medical Center, Nashville, 37232-6307, TN, USA.
Yao LuDepartments of Medicine, Vanderbilt University Medical Center, Nashville, 37232-6307, TN, USA.
Alberto ServettoUTSW Simmons Cancer Center, Dallas, TX, 75230, USA.
Ariella B HankerDepartments of Medicine, Vanderbilt University Medical Center, Nashville, 37232-6307, TN, USA.ORCID http://orcid.org/0000-0002-8655-8341
Valerie M JansenDepartments of Medicine, Vanderbilt University Medical Center, Nashville, 37232-6307, TN, USA.
Joshua A BauerDepartments of Biochemistry, Vanderbilt University Medical Center, Nashville, 37232-6307, TN, USA.
Dhivya R SudhanDepartments of Medicine, Vanderbilt University Medical Center, Nashville, 37232-6307, TN, USA.
Angel L Guerrero-ZotanoDepartments of Medicine, Vanderbilt University Medical Center, Nashville, 37232-6307, TN, USA.ORCID http://orcid.org/0000-0003-0318-9120
Sarah CroessmannDepartments of Medicine, Vanderbilt University Medical Center, Nashville, 37232-6307, TN, USA.
Yan GuoVanderbilt Center for Quantitative Sciences, Vanderbilt University School of Medicine, Nashville, 37232-6307, TN, USA.
Paula Gonzalez EricssonBreast Cancer Program, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, 37232-6307, TN, USA.ORCID http://orcid.org/0000-0002-6292-6963
Kyung-Min LeeDepartments of Medicine, Vanderbilt University Medical Center, Nashville, 37232-6307, TN, USA.
Mellissa J NixonDepartments of Medicine, Vanderbilt University Medical Center, Nashville, 37232-6307, TN, USA.
Luis J SchwarzDepartments of Medicine, Vanderbilt University Medical Center, Nashville, 37232-6307, TN, USA.
Melinda E SandersBreast Cancer Program, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, 37232-6307, TN, USA.
Teresa C DuggerDepartments of Medicine, Vanderbilt University Medical Center, Nashville, 37232-6307, TN, USA.
Marcelo Rocha CruzRobert H Lurie Comprehensive Cancer Center, Chicago, 60611, IL, USA.
Amir BehdadRobert H Lurie Comprehensive Cancer Center, Chicago, 60611, IL, USA.
Massimo CristofanilliRobert H Lurie Comprehensive Cancer Center, Chicago, 60611, IL, USA.
Aditya BardiaMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, 02114, MA, USA.
Joyce O'ShaughnessyBaylor University Medical Center, Texas Oncology, , US Oncology, Dallas, 75246, TX, USA.
Rebecca J NagyGuardant Health, Redwood City, 94063, CA, USA.
Richard B LanmanGuardant Health, Redwood City, 94063, CA, USA.ORCID http://orcid.org/0000-0001-8122-4329
Nadia SolovieffNovartis Institutes for Biomedical Research, Cambridge, 02139, MA, USA.
Wei HeNovartis Institutes for Biomedical Research, Cambridge, 02139, MA, USA.
Michelle MillerNovartis Pharmaceuticals Corporation, East Hanover, 07936, NJ, USA.
Fei SuNovartis Pharmaceuticals Corporation, East Hanover, 07936, NJ, USA.
Yu ShyrVanderbilt Center for Quantitative Sciences, Vanderbilt University School of Medicine, Nashville, 37232-6307, TN, USA.
Ingrid A MayerDepartments of Medicine, Vanderbilt University Medical Center, Nashville, 37232-6307, TN, USA.
Justin M BalkoDepartments of Medicine, Vanderbilt University Medical Center, Nashville, 37232-6307, TN, USA.ORCID http://orcid.org/0000-0002-4263-5974
Carlos L ArteagaDepartments of Medicine, Vanderbilt University Medical Center, Nashville, 37232-6307, TN, USA. carlos.arteaga@utsouthwestern.edu.
Vanderbilt University Medical Center · USNovartis (United States) · USHarold C. Simmons Comprehensive Cancer CenterIndo-American Center · USGuardant (United States) · USVanderbilt University · USBreast Cancer Research Foundation · USHarvard University · USTexas Oncology · US

Funding

Tumor Immunology and Microenvironment Research ProgramP30CA068485 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI MATTHEW J TYSKA · 1995 to 2026
$172.8M
TISSUE CoreP50CA098131 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI PARK, BEN HO, PIETENPOL, JENNIFER A · 2003 to 2024
$48.7M
Vanderbilt Clinical Oncology Research Career Development ProgramK12CA090625 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Debra L. Friedman, Paula Jill Hurley · 2001 to 2026
$16.9M
Paul Calabresi Clinical Oncology AwardK12CA088084 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI David S. Hong, Scott Kopetz · 2000 to 2026
$14.0M
Cancer Pharmacologist and HTS ScientistR50CA211206 · NCI · VANDERBILT UNIVERSITY · PI Joshua A. Bauer · 2016 to 2026
$1.8M
NCI NIH HHS K12 CA088084NCI NIH HHS K12 CA090625NCI NIH HHS P30 CA068485NCI NIH HHS P50 CA098131NCI NIH HHS R50 CA211206
6 · The paper itself

Abstract

Using an ORF kinome screen in MCF-7 cells treated with the CDK4/6 inhibitor ribociclib plus fulvestrant, we identified FGFR1 as a mechanism of drug resistance. FGFR1-amplified/ER+ breast cancer cells and MCF-7 cells transduced with FGFR1 were resistant to fulvestrant ± ribociclib or palbociclib. This resistance was abrogated by treatment with the FGFR tyrosine kinase inhibitor (TKI) lucitanib. Addition of the FGFR TKI erdafitinib to palbociclib/fulvestrant induced complete responses of FGFR1-amplified/ER+ patient-derived-xenografts. Next generation sequencing of circulating tumor DNA (ctDNA) in 34 patients after progression on CDK4/6 inhibitors identified FGFR1/2 amplification or activating mutations in 14/34 (41%) post-progression specimens. Finally, ctDNA from patients enrolled in MONALEESA-2, the registration trial of ribociclib, showed that patients with FGFR1 amplification exhibited a shorter progression-free survival compared to patients with wild type FGFR1. Thus, we propose breast cancers with FGFR pathway alterations should be considered for trials using combinations of ER, CDK4/6 and FGFR antagonists.

Indexed as

AminopyridinesAnimalsAntineoplastic Agents, HormonalAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsCirculating Tumor DNACyclin D1Cyclin-Dependent Kinase 4Cyclin-Dependent Kinase 6Drug Resistance, NeoplasmFemaleFulvestrantHigh-Throughput Nucleotide SequencingHumansMCF-7 CellsMiceAminopyridinesAntineoplastic Agents, HormonalCCND1 protein, humanCirculating Tumor DNACyclin D1Cyclin-Dependent Kinase 4Cyclin-Dependent Kinase 6E-3810erdafitinibFGFR1 protein, humanFGFR2 protein, humanFulvestrantNaphthalenespalbociclibPiperazinesProtein Kinase InhibitorsPurinesPyrazolesPyridinesQuinolinesQuinoxalinesReceptor, Fibroblast Growth Factor, Type 1Receptor, Fibroblast Growth Factor, Type 2Receptors, Estrogenribociclib

Identifiers

PMID30914635
PMCPMC6435685
OpenAlexW2925017918

What OpenQuestion holds

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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.