Evidence map›Paper›PMID 31586042›Full record

ArticleOncogenesis2019

CtBP-a targetable dependency for tumor-initiating cell activity and metastasis in pancreatic adenocarcinoma.

Ayesha T Chawla, Kranthi Kumar Chougoni, Prashant J Joshi, Agnes D Cororaton, Patrick Memari, John C Stansfield, Haemin Park, Rashmi Seth, Barbara Szomju, Adam P Sima and 3 more

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

Article in Oncogenesis, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.0field-weighted citation impact, top 24% 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

15 citing papers in PubMed, 67 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Review
  11. Cryo-EM structure of CtBP2 confirms tetrameric architecture.Structure (London, England : 1993) · 2021
    Article
  12. Review
  13. Article
  14. Article
  15. 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

13 authors at 1 institution in 1 country.

Ayesha T ChawlaC. Kenneth and Diane Wright Center for Clinical and Translational Research, Virginia Commonwealth University, Richmond, VA, 23298, USA.
Kranthi Kumar ChougoniC. Kenneth and Diane Wright Center for Clinical and Translational Research, Virginia Commonwealth University, Richmond, VA, 23298, USA.
Prashant J JoshiDepartment of Internal Medicine, Virginia Commonwealth University, Richmond, VA, 23298, USA.
Agnes D CororatonDepartment of Internal Medicine, Virginia Commonwealth University, Richmond, VA, 23298, USA.
Patrick MemariDepartment of Pathology, Virginia Commonwealth University, Richmond, VA, 23298, USA.
John C StansfieldDepartment of Biostatistics, Virginia Commonwealth University, Richmond, VA, 23298, USA.
Haemin ParkDepartment of Internal Medicine, Virginia Commonwealth University, Richmond, VA, 23298, USA.
Rashmi SethDepartment of Surgery, Virginia Commonwealth University, Richmond, VA, 23298, USA.
Barbara SzomjuDepartment of Internal Medicine, Virginia Commonwealth University, Richmond, VA, 23298, USA.
Adam P SimaDepartment of Biostatistics, Virginia Commonwealth University, Richmond, VA, 23298, USA.ORCID http://orcid.org/0000-0001-8426-9987
Michael O IdowuDepartment of Pathology, Virginia Commonwealth University, Richmond, VA, 23298, USA.
Keith C EllisVCU Massey Cancer Center, Virginia Commonwealth University, Richmond, VA, 23298, USA.
Steven R GrossmanDepartment of Internal Medicine, Virginia Commonwealth University, Richmond, VA, 23298, USA. steven.grossman@vcuhealth.org.
Virginia Commonwealth University · US

Funding

Virus Vector Shared ResourceP30CA016059 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI Kim Felder Rhoads · 1985 to 2026
$51.0M
NCI NIH HHS P30 CA016059
6 · The paper itself

Abstract

Ctbp2 is a uniquely targetable oncogenic transcriptional coregulator, exhibiting overexpression in most common solid tumors, and critical to the tumor-initiating cell (TIC) transcriptional program. In the "CKP" mouse pancreatic ductal adenocarcinoma (PDAC) model driven by mutant K-Ras, Ctbp2 haploinsufficiency prolonged survival, abrogated peritoneal metastasis, and caused dramatic downregulation of c-Myc, a known critical dependency for TIC activity and tumor progression in PDAC. A small-molecule inhibitor of CtBP2, 4-chloro-hydroxyimino phenylpyruvate (4-Cl-HIPP) phenocopied Ctbp2 deletion, decreasing tumor burden similarly to gemcitabine, and the combination of 4-Cl-HIPP and gemcitabine further synergistically suppressed tumor growth. Pharmacodynamic monitoring revealed that the 4-Cl-HIPP/gemcitabine combination induced robust and synergistic tumor apoptosis and marked downregulation of the TIC marker CD133 in CKP PDAC tumors. Collectively, our data demonstrate that targeting CtBP represents a fruitful avenue for development of highly active agents in PDAC that cooperate with standard therapy to limit both primary and metastatic tumor burden.

Identifiers

PMID31586042
PMCPMC6778071
OpenAlexW2978556114

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.