Evidence map›Paper›PMID 33334024›Full record

ArticleCancers2020

Matrix Drug Screen Identifies Synergistic Drug Combinations to Augment SMAC Mimetic Activity in Ovarian Cancer.

Anne M Noonan, Amanda Cousins, David Anderson, Kristen P Zeligs, Kristen Bunch, Lidia Hernandez, Yusuke Shibuya, Ian S Goldlust, Rajarshi Guha, Marc Ferrer and 2 more

Open access · goldAbstract read
In one paragraph

Article in Cancers, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.3field-weighted citation impact, top 45% 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

9 citing papers in PubMed, 8 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. BH3-mimetics: recent developments in cancer therapy.Journal of experimental & clinical cancer research : CR · 2021
    Review
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

12 authors at 1 institution in 1 country.

Anne M NoonanWomen's Malignancies Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Amanda CousinsWomen's Malignancies Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
David AndersonWomen's Malignancies Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Kristen P ZeligsWomen's Malignancies Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.ORCID 0000-0003-4191-5154
Kristen BunchWomen's Malignancies Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Lidia HernandezWomen's Malignancies Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Yusuke ShibuyaWomen's Malignancies Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.ORCID 0000-0001-9295-4108
Ian S GoldlustThe National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892, USA.
Rajarshi GuhaThe National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892, USA.
Marc FerrerThe National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892, USA.
Craig J ThomasThe National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892, USA.
Christina M AnnunziataWomen's Malignancies Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.ORCID 0000-0003-2033-6532
National Institutes of Health · US

Funding

National Cancer Institute USA BC011054National Center for Advancing Translational Sciences TR000047Rivkin Ovarian Cancer Foundation n/a
6 · The paper itself

Abstract

Inhibitor of apoptosis (IAP) proteins are frequently upregulated in ovarian cancer, resulting in the evasion of apoptosis and enhanced cellular survival. Birinapant, a synthetic second mitochondrial activator of caspases (SMAC) mimetic, suppresses the functions of IAP proteins in order to enhance apoptotic pathways and facilitate tumor death. Despite on-target activity, however, pre-clinical trials of single-agent birinapant have exhibited minimal activity in the recurrent ovarian cancer setting. To augment the therapeutic potential of birinapant, we utilized a high-throughput screening matrix to identify synergistic drug combinations. Of those combinations identified, birinapant plus docetaxel was selected for further evaluation, given its remarkable synergy both in vitro and in vivo. We showed that this synergy results from multiple convergent pathways to include increased caspase activation, docetaxel-mediated TNF-α upregulation, alternative NF-kB signaling, and birinapant-induced microtubule stabilization. These findings provide a rationale for the integration of birinapant and docetaxel in a phase 2 clinical trial for recurrent ovarian cancer where treatment options are often limited and minimally effective.

Indexed as

birinapantdocetaxelmicrotubule stabilityNF-kBovarian cancerSMAC mimeticssynergyTNF-α

Identifiers

PMID33334024
PMCPMC7765376
OpenAlexW3112931730

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.