Evidence mapPaperPMID 38643482Full record

ReviewEndocrinology2024

Estrogen Receptor Alpha Mutations, Truncations, Heterodimers, and Therapies.

Govinda R Hancock, Jason Gertz, Rinath Jeselsohn, Sean W Fanning

Open access · bronzeAbstract readReview
In one paragraph

Review in Endocrinology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
9.9field-weighted citation impact, top 2% 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

14 citing papers in PubMed, 18 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Review
  9. Harnessing the Role ofInternational journal of molecular sciences · 2025
    Article
  10. Review
  11. Review
  12. Review
  13. Article
  14. Article
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

4 authors at 3 institutions in 1 country.

Govinda R HancockDepartment of Cancer Biology, Loyola University Chicago Stritch School of Medicine, Maywood, IL 60513, USA.ORCID 0000-0002-3384-7983
Jason GertzDepartment of Oncological Sciences, Huntsman Cancer Center, University of Utah, Salt Lake City, UT 84112, USA.ORCID 0000-0001-7568-6789
Rinath JeselsohnDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Sean W FanningDepartment of Cancer Biology, Loyola University Chicago Stritch School of Medicine, Maywood, IL 60513, USA.ORCID 0000-0002-9428-0060
Loyola University Chicago · USBrigham and Women's Hospital · USUniversity of Utah · US

Funding

Structural-Transcriptional Relationships that Improve Y537S Estrogen Receptor AntagonismR37CA279341 · LOYOLA UNIVERSITY CHICAGO · 2025 to 2025
$345k
NCI NIH HHS R37 CA279341NIH HHS
6 · The paper itself

Abstract

Annual breast cancer (BCa) deaths have declined since its apex in 1989 concomitant with widespread adoption of hormone therapies that target estrogen receptor alpha (ERα), the prominent nuclear receptor expressed in ∼80% of BCa. However, up to ∼50% of patients who are ER+ with high-risk disease experience post endocrine therapy relapse and metastasis to distant organs. The vast majority of BCa mortality occurs in this setting, highlighting the inadequacy of current therapies. Genomic abnormalities to ESR1, the gene encoding ERα, emerge under prolonged selective pressure to enable endocrine therapy resistance. These genetic lesions include focal gene amplifications, hotspot missense mutations in the ligand binding domain, truncations, fusions, and complex interactions with other nuclear receptors. Tumor cells utilize aberrant ERα activity to proliferate, spread, and evade therapy in BCa as well as other cancers. Cutting edge studies on ERα structural and transcriptional relationships are being harnessed to produce new therapies that have shown benefits in patients with ESR1 hotspot mutations. In this review we discuss the history of ERα, current research unlocking unknown aspects of ERα signaling including the structural basis for receptor antagonism, and future directions of ESR1 investigation. In addition, we discuss the development of endocrine therapies from their inception to present day and survey new avenues of drug development to improve pharmaceutical profiles, targeting, and efficacy.

Indexed as

Breast NeoplasmsEstrogen Receptor alphaMutationAnimalsAntineoplastic Agents, HormonalFemaleHumansAntineoplastic Agents, HormonalESR1 protein, humanEstrogen Receptor alphabreast cancerendocrine therapyERα antagonismESR1hotspot mutationsstructural variants

Identifiers

PMID38643482
PMCPMC11075793
OpenAlexW4394984706

What Socratic holds

Textmetadata
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 Socratic graph.