Evidence map›Paper›PMID 26271487›Full record

ArticleMolecular cancer research : MCR2015

Downregulation of Critical Oncogenes by the Selective SK2 Inhibitor ABC294640 Hinders Prostate Cancer Progression.

Randy S Schrecengost, Staci N Keller, Matthew J Schiewer, Karen E Knudsen, Charles D Smith

Abstract read
In one paragraph

Article in Molecular cancer research : MCR, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
3.3field-weighted citation impact, top 7% 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

35 citing papers in PubMed, 43 citations in OpenAlex.

  1. Trial
  2. Review
  3. Opaganib Protects Against High-Fat Diet-Induced Hypercholesterolemia and Liver Steatosis in Mice.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026
    Article
  4. Opaganib Promotes Weight Loss and Suppresses High-Fat Diet-Induced Obesity and Glucose Intolerance.Diabetes, metabolic syndrome and obesity : targets and therapy · 2025
    Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. The Sphingosine Kinase 2 Inhibitor Opaganib Protects Against Acute Kidney Injury in Mice.International journal of nephrology and renovascular disease · 2022
    Article
  14. Review
  15. Targeting Sphingolipids for Cancer Therapy.Frontiers in oncology · 2021
    Review
  16. Article
  17. Article
  18. Article
  19. Review
  20. 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

5 authors at 2 institutions in 1 country.

Randy S SchrecengostApogee Biotechnology Corporation, Hummelstown, Pennsylvania.
Staci N KellerApogee Biotechnology Corporation, Hummelstown, Pennsylvania.
Matthew J SchiewerDepartment of Cancer Biology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.
Karen E KnudsenDepartment of Cancer Biology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania. Department of Urology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania. Department of Radiation Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.
Charles D SmithApogee Biotechnology Corporation, Hummelstown, Pennsylvania. cdsmith@apogee-biotech.com.
Sidney Kimmel Cancer Center · USThomas Jefferson University · US

Funding

Radiosensitizing Prostate Cancer by Downregulation of Androgen Receptors and c-MycR43CA192414 · NCI · APOGEE BIOTECHNOLOGY CORPORATION · PI SCHRECENGOST, RANDY · 2015 to 2015
$225k
NCI NIH HHS R43 CA192414
6 · The paper itself

Abstract

unlabelledThe bioactive sphingolipid sphingosine-1-phosphate (S1P) drives several hallmark processes of cancer, making the enzymes that synthesize S1P, that is, sphingosine kinase 1 and 2 (SK1 and SK2), important molecular targets for cancer drug development. ABC294640 is a first-in-class SK2 small-molecule inhibitor that effectively inhibits cancer cell growth in vitro and in vivo. Given that AR and Myc are two of the most widely implicated oncogenes in prostate cancer, and that sphingolipids affect signaling by both proteins, the therapeutic potential for using ABC294640 in the treatment of prostate cancer was evaluated. This study demonstrates that ABC294640 abrogates signaling pathways requisite for prostate cancer growth and proliferation. Key findings validate that ABC294640 treatment of early-stage and advanced prostate cancer models downregulate Myc and AR expression and activity. This corresponds with significant inhibition of growth, proliferation, and cell-cycle progression. Finally, oral administration of ABC294640 was found to dramatically impede xenograft tumor growth. Together, these pre-clinical findings support the hypotheses that SK2 activity is required for prostate cancer function and that ABC294640 represents a new pharmacological agent for treatment of early stage and aggressive prostate cancer. IMPLICATIONS: Sphingosine kinase inhibition disrupts multiple oncogenic signaling pathways that are deregulated in prostate cancer.

Indexed as

Down-RegulationAdamantaneAnimalsAntineoplastic AgentsCell Line, TumorDisease ProgressionGene Expression Regulation, NeoplasticHumansMaleMiceProstatic NeoplasmsProto-Oncogene Proteins c-mycPyridinesReceptors, AndrogenSignal TransductionSmall-Conductance Calcium-Activated Potassium Channels3-(4-chlorophenyl)-adamantane-1-carboxylic acid (pyridin-4-ylmethyl)amideAdamantaneAntineoplastic AgentsAR protein, humanKCNN2 protein, humanMYC protein, humanProto-Oncogene Proteins c-mycPyridinesReceptors, AndrogenSmall-Conductance Calcium-Activated Potassium Channels

Identifiers

PMID26271487
PMCPMC4685021
OpenAlexW1777295695

What OpenQuestion holds

Textmetadata
LicenceTDM
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.