Evidence map›Paper›PMID 27750219›Full record

ReviewOncotarget2017

Improving anticancer drug development begins with cell culture: misinformation perpetrated by the misuse of cytotoxicity assays.

Alan Eastman

Abstract readReview
In one paragraph

Review in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.

0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed
–field-weighted citation impact
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

60 citing papers in PubMed.

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  20. PINK1 regulates apoptosis of osteosarcoma as the target gene of cisplatin.Journal of orthopaedic surgery and research · 2023
    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

1 author.

Alan EastmanNorris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA.

Funding

Mechanisms of Sensitivity to Cell Cycle Checkpoint Kinase InhibitorsR01CA117874 · NCI · DARTMOUTH COLLEGE · PI EASTMAN, ALAN R · 2007 to 2017
$3.0M
NCI NIH HHS R01 CA117874
6 · The paper itself

Abstract

The high failure rate of anticancer drug discovery and development has consumed billions of dollars annually. While many explanations have been provided, I believe that misinformation arising from inappropriate cell-based screens has been completely over-looked. Most cell culture experiments are irrelevant to how drugs are subsequently administered to patients. Usually, drug development focuses on growth inhibition rather than cell killing. Drugs are selected based on continuous incubation of cells, then frequently administered to the patient as a bolus. Target identification and validation is often performed by gene suppression that inevitably mimics continuous target inhibition. Drug concentrations in vitro frequently far exceed in vivo concentrations. Studies of drug synergy are performed at sub-optimal concentrations. And the focus on a limited number of cell lines can misrepresent the potential efficacy in a patient population. The intent of this review is to encourage more appropriate experimental design and data interpretation, and to improve drug development in the area of cell-based assays. Application of these principles should greatly enhance the successful translation of novel drugs to the patient.

Indexed as

Biological AssayAnimalsAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsCell DeathCell Line, TumorCell ProliferationCell SurvivalDose-Response Relationship, DrugDrug DiscoveryDrug SynergismGene Expression Regulation, NeoplasticGene Knockdown TechniquesHumansNeoplasmsReproducibility of ResultsAntineoplastic Agentsapoptosiscell survivalcytotoxicity assayssynergytarget validation

Identifiers

PMID27750219
PMCPMC5352448

What OpenQuestion holds

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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.