Evidence map›Paper›PMID 31367787›Full record

ArticleCancer chemotherapy and pharmacology2019

Identification of pharmacodynamic biomarkers and common molecular mechanisms of response to genotoxic agents in cancer cell lines.

Dong-Joon Min, Yingdong Zhao, Anne Monks, Alida Palmisano, Curtis Hose, Beverly A Teicher, James H Doroshow, Richard M Simon

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer chemotherapy and pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.5field-weighted citation impact, top 40% 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

6 citing papers in PubMed, 9 citations in OpenAlex.

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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

8 authors at 3 institutions in 1 country.

Dong-Joon MinBiometric Research Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, 9609 Medical Center Dr., Rockville, MD, 20850, USA.
Yingdong ZhaoBiometric Research Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, 9609 Medical Center Dr., Rockville, MD, 20850, USA.
Anne MonksMolecular Pharmacology Group, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, 21702, USA.
Alida PalmisanoBiometric Research Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, 9609 Medical Center Dr., Rockville, MD, 20850, USA.
Curtis HoseMolecular Pharmacology Group, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, 21702, USA.
Beverly A TeicherDevelopmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD, 20892, USA.
James H DoroshowDivision of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD, 20892, USA.
Richard M SimonBiometric Research Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, 9609 Medical Center Dr., Rockville, MD, 20850, USA. richard.simon@nih.gov.
National Cancer Institute · USFrederick National Laboratory for Cancer Research · USLeidos (United States) · US

Funding

NADPH Oxidase 1: A Novel Target for Colon Cancer TherapyZ01BC010677 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI DOROSHOW, JAMES HALPERN · 2005 to 2008
$1.1M
CCR NIH HHS HHSN261200800001CIntramural NIH HHS Z01 BC010677NCI NIH HHS HHSN261200800001E
6 · The paper itself

Abstract

purposeGenotoxic agents (GAs) including cisplatin, doxorubicin, gemcitabine, and topotecan are often used in cancer treatment. However, the response to GAs is variable among patients and predictive biomarkers are inadequate to select patients for treatment. Accurate and rapid pharmacodynamics measures of response can, thus, be useful for monitoring therapy and improve clinical outcomes.

methodsThis study focuses on integrating a database of genome-wide response to treatment (The NCI Transcriptional Pharmacodynamics Workbench) with a database of baseline gene expression (GSE32474) for the NCI-60 cell lines to identify mechanisms of response and pharmacodynamic (PD) biomarkers. RESULTS AND

conclusionsOur analysis suggests that GA-induced endoplasmic reticulum (ER) stress may signal for GA-induced cell death. Reducing the uptake of GA, activating DNA repair, and blocking ER-stress induction cooperate to prevent GA-induced cell death in the GA-resistant cells. ATF3, DDIT3, CARS, and PPP1R15A appear as possible candidate PD biomarkers for monitoring the progress of GA treatment. Further validation studies on the proposed intrinsic drug-resistant mechanism and candidate genes are needed using in vivo data from either patient-derived xenograft models or clinical chemotherapy trials.

Indexed as

Cell DeathDNA DamageEndoplasmic Reticulum StressActivating Transcription Factor 3Antineoplastic AgentsBiomarkers, PharmacologicalCell Line, TumorDrug Resistance, NeoplasmGene Expression ProfilingGenome-Wide Association StudyHumansMutagensProtein Phosphatase 1ROC CurveTranscription Factor CHOPActivating Transcription Factor 3Antineoplastic AgentsATF3 protein, humanBiomarkers, PharmacologicalDDIT3 protein, humanMutagensPPP1R15A protein, humanProtein Phosphatase 1Transcription Factor CHOPER stressGenotoxic agentsPharmacodynamic biomarkersResponse mechanisms

Identifiers

PMID31367787
PMCPMC8127867
OpenAlexW2966603567

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.