Evidence map›Paper›PMID 33000123›Full record

ArticleThe Journal of clinical endocrinology and metabolism2021

Targeting Corticotroph HDAC and PI3-Kinase in Cushing Disease.

Dongyun Zhang, Robert Damoiseaux, Lilit Babayan, Everett Kanediel Rivera-Meza, Yingying Yang, Marvin Bergsneider, Marilene B Wang, William H Yong, Kathleen Kelly, Anthony P Heaney

Erratum issuedOpen access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of clinical endocrinology and metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
0.8field-weighted citation impact, top 30% 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

11 citing papers in PubMed, 27 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Advances in pharmacological treatment of CushingZhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2024
    Review
  5. Article
  6. Review
  7. Article
  8. Treatment of Cushing Disease With Pituitary-Targeting Seliciclib.The Journal of clinical endocrinology and metabolism · 2023
    Article
  9. Article
  10. Article
  11. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 1 institution in 1 country.

Dongyun ZhangDepartment of Medicine, University of California, David Geffen School of Medicine, Los Angeles, California.
Robert DamoiseauxDepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, California.
Lilit BabayanDepartment of Medicine, University of California, David Geffen School of Medicine, Los Angeles, California.
Everett Kanediel Rivera-MezaDepartment of Medicine, University of California, David Geffen School of Medicine, Los Angeles, California.
Yingying YangDepartment of Medicine, University of California, David Geffen School of Medicine, Los Angeles, California.
Marvin BergsneiderDepartment of Neurosurgery, David Geffen School of Medicine, University of California, Los Angeles, California.
Marilene B WangDepartment of Head and Neck Surgery, David Geffen School of Medicine, University of California, Los Angeles, California.
William H YongDepartment of Pathology and Lab Medicine, David Geffen School of Medicine, University of California, Los Angeles, California.
Kathleen KellyDepartment of Pathology and Lab Medicine, David Geffen School of Medicine, University of California, Los Angeles, California.
Anthony P HeaneyDepartment of Medicine, University of California, David Geffen School of Medicine, Los Angeles, California.
University of California, Los Angeles · US

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Samuel Wheeler French · 1985 to 2026
$134.5M
UCLA SPORE in Brain CancerP50CA211015 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Yvonne Yu-Hsuan Chen · 2017 to 2026
$25.2M
NCI NIH HHS P30 CA016042NCI NIH HHS P50 CA211015
6 · The paper itself

Abstract

contextCushing disease (CD) is a life-threatening disorder. Therapeutic goals include symptom relief, biochemical control, and tumor growth inhibition. Current medical therapies for CD by and large exert no action on tumor growth.

objectiveTo identify drugs that inhibit corticotroph tumor adrenocorticotropic hormone (ACTH) secretion and growth.

designHigh throughput screen employing a novel "gain of signal" ACTH AlphaLISA assay.

settingAcademic medical center. PATIENTS: Corticotroph tumor tissues from patients with CD.

interventionsNone.

main outcome measuresPotent inhibitors of corticotroph tumor ACTH secretion and growth.

resultsFrom a kinase inhibitor library, we identified the dual PI3K/HDAC inhibitor CUDC-907 as a potent inhibitor of murine and human corticotroph tumor ACTH secretion (median effective concentration 1-5 nM), and cell proliferation (median inhibitory concentration 5 nM). In an in vivo murine corticotroph tumor xenograft model, orally administered CUDC-907 (300 mg/kg) reduced corticotroph tumor volume (TV [cm3], control 0.17 ± 0.05 vs CUDC-907 0.07 ± 0.02, P < .05) by 65% and suppressed plasma ACTH (ACTH [pg/mL] control 206 ± 27 vs CUDC-907 47 ± 7, P < .05) and corticosterone (corticosterone [ng/mL] control 180 ± 87 vs CUDC-907 27 ± 5, P < .05) levels by 77% and 85% respectively compared with controls. We also demonstrated that CUDC-907 acts through HDAC1/2 inhibition at the proopiomelanocortin transcriptional level combined with its PI3K-mediated inhibition of corticotroph cell viability to reduce ACTH secretion.

conclusionsGiven its potent efficacy in in vitro and in vivo models of CD, combined with proven safety and tolerance in clinical trials, we propose CUDC-907 may be a promising therapy for CD.

Indexed as

ACTH-Secreting Pituitary AdenomaAdenomaAdrenocorticotropic HormoneAnimalsAntineoplastic AgentsCell ProliferationCorticotrophsGene Expression Regulation, NeoplasticHigh-Throughput Screening AssaysHistone Deacetylase InhibitorsHumansMiceMice, NudeMolecular Targeted TherapyMorpholinesPhosphoinositide-3 Kinase InhibitorsAdrenocorticotropic HormoneAntineoplastic AgentsCUDC-907Histone Deacetylase InhibitorsMorpholinesPhosphoinositide-3 Kinase InhibitorsPyrimidinesadrenocorticotropic hormoneamplified luminescent proximity homogeneous assayCUDC-907 (fimeprinostat)Cushing diseasehigh throughput screenhistone deacetylasephosphoinositide 3-kinasepituitary adenoma

Identifiers

PMID33000123
PMCPMC8921634
OpenAlexW3090331344

What OpenQuestion 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 OpenQuestion graph.