Evidence map›Paper›PMID 24076266›Full record

ReviewPharmacology & therapeutics2014

Targeting notch signaling pathway in cancer: clinical development advances and challenges.

Naoko Takebe, Dat Nguyen, Sherry X Yang

Open access · greenAbstract readReview
In one paragraph

Review in Pharmacology & therapeutics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 229 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
229citing papers in PubMed, 1 pooled it
49.3field-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

229 citing papers in PubMed, 1 synthesis or guideline pooled it, 401 citations in OpenAlex.

  1. Pooled it
  2. Nirogacestat, a γ-Secretase Inhibitor for Desmoid Tumors.The New England journal of medicine · 2023
    Trial
  3. Trial
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Review
  14. Review
  15. Review
  16. Review
  17. Article
  18. Review
  19. Review
  20. Review

169 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

3 authors at 1 institution in 1 country.

Naoko TakebeCancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, Bethesda, United States. Electronic address: takeben@mail.nih.gov.
Dat NguyenNational Clinical Target Validation Laboratory, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, Bethesda, United States.
Sherry X YangNational Clinical Target Validation Laboratory, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, Bethesda, United States. Electronic address: Sherry.Yang@nih.gov.
National Institutes of Health · US

Funding

Intramural NIH HHS Z99 CA999999
6 · The paper itself

Abstract

Notch signaling plays an important role in development and cell fate determination, and it is deregulated in human hematologic malignancies and solid tumors. This review includes a brief introduction of the relevant pathophysiology of Notch signaling pathway and primarily focuses on the clinical development of promising agents that either obstruct Notch receptor cleavages such as γ-secretase inhibitors (GSIs) or interfere with the Notch ligand-receptor interaction by monoclonal antibodies (mAbs). Antitumor activity by GSIs and mAbs administered as single agent in early phases of clinical trials has been observed in advanced or metastatic thyroid cancer, non-small cell lung cancer, intracranial tumors, sarcoma or desmoid tumors, colorectal cancer with neuroendocrine features, melanoma and ovarian cancer. A number of mechanism-based adverse events particularly gastrointestinal toxicities emerged and mitigation strategies are developed after testing multiple GSIs and Notch targeting mAbs. We also discuss pharmacodynamic biomarkers in conjunction with methods of assessment of the molecular target inhibition validation. Biomarkers of efficacy or benefit may be of importance for a successful development of this class of drugs.

Indexed as

AnimalsAntineoplastic AgentsBiomarkersHumansNeoplasmsNeoplastic Stem CellsNeovascularization, PathologicReceptors, NotchSignal TransductionAntineoplastic AgentsBiomarkersReceptors, NotchADAMa disintegrin and metalloproteasesBiomarkerscancer stem cellsClinical trialscomplete responseCRCSCsDelta-like ligandDiarrheaDLLDLTdose limiting toxicityEDTAethylenediaminetetraacetic acidGBMglioblastoma multiformeGSIJAGJaggedmAbMAMLmammosphere-forming efficiencymastermind-likemaximum tolerated dosemetalloproteinase tumor necrosis factor-α-converting enzymeMonoclonal antibodies (mAbs)monoclonal antibodyMSFEMTDNICDnon-small cell lung cancerNotch intracellular domainNotch signalingNSCLCpartial responsePDpharmacodynamicspharmacokineticsPKPRRECISTresponse evaluation criteria in solid tumorsSDstable diseaseTACET-ALLT-cell acute lymphoblastic leukemiaT-cell lymphoblastic lymphomaTICsT-LLtumor initiating cellsγ-secretase inhibitorγ-Secretase inhibitors

Identifiers

PMID24076266
PMCPMC3982918
OpenAlexW2019708706

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.