Evidence map›Paper›PMID 34606726›Full record

ArticleJournal of medicinal chemistry2021

Inhibitor Combinations Reveal Wiring of the Proteostasis Network in Prostate Cancer Cells.

Arielle Shkedi, Michael Adkisson, Andrew Schroeder, Walter L Eckalbar, Szu-Yu Kuo, Leonard Neckers, Jason E Gestwicki

Open access · greenAbstract read
In one paragraph

Article in Journal of medicinal chemistry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.2field-weighted citation impact, top 47% 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

2 citing papers in PubMed, 5 citations in OpenAlex.

  1. Article
  2. 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

7 authors at 2 institutions in 1 country.

Arielle ShkediDepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California 94158, United States.
Michael AdkissonFunctional Genomics Core, University of California San Francisco, San Francisco, California 94158, United States.
Andrew SchroederFunctional Genomics Core, University of California San Francisco, San Francisco, California 94158, United States.
Walter L EckalbarFunctional Genomics Core, University of California San Francisco, San Francisco, California 94158, United States.
Szu-Yu KuoDepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California 94158, United States.
Leonard NeckersUrologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, United States.
Jason E GestwickiDepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California 94158, United States.ORCID 0000-0002-6125-3154
University of California, San Francisco · USNational Cancer Institute · US

Funding

Molecular Chaperones and Small MoleculesR01NS059690 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Jason E Gestwicki · 2008 to 2026
$7.9M
PHARMACEUTICAL SCIENCES AND PHARMACOGENOMICST32GM007175 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI AHITUV, NADAV, KROETZ, DEANNA L · 1985 to 2021
$7.1M
NIGMS NIH HHS T32 GM007175NINDS NIH HHS R01 NS059690
6 · The paper itself

Abstract

The protein homeostasis (proteostasis) network is composed of multiple pathways that work together to balance protein folding, stability, and turnover. Cancer cells are particularly reliant on this network; however, it is hypothesized that inhibition of one node might lead to compensation. To better understand these connections, we dosed 22Rv1 prostate cancer cells with inhibitors of four proteostasis targets (Hsp70, Hsp90, proteasome, and p97), either alone or in binary combinations, and measured the effects on cell growth. The results reveal a series of additive, synergistic, and antagonistic relationships, including strong synergy between inhibitors of p97 and the proteasome and striking antagonism between inhibitors of Hsp90 and the proteasome. Based on RNA-seq, these relationships are associated, in part, with activation of stress pathways. Together, these results suggest that cocktails of proteostasis inhibitors might be a powerful way of treating some cancers, although antagonism that blunts the efficacy of both molecules is also possible.

Indexed as

Antineoplastic AgentsCell Line, TumorCell SurvivalHSP70 Heat-Shock ProteinsHSP90 Heat-Shock ProteinsHumansMaleProstatic NeoplasmsProteasome Endopeptidase ComplexProteostasisReceptors, AndrogenSequence Analysis, RNAStress, PhysiologicalAntineoplastic AgentsAR protein, humanHSP70 Heat-Shock ProteinsHSP90 Heat-Shock ProteinsProteasome Endopeptidase ComplexReceptors, Androgen

Identifiers

PMID34606726
PMCPMC8806517
OpenAlexW3202338036

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.