Evidence map›Paper›PMID 26362996›Full record

ReviewClinical cancer research : an official journal of the American Association for Cancer Research2015

Molecular Pathways: Targeting ATR in Cancer Therapy.

Larry M Karnitz, Lee Zou

Abstract readReview
In one paragraph

Review in Clinical cancer research : an official journal of the American Association for Cancer Research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 184 papers.

0numbers the graph read from it
0cells of the map it votes in
184citing papers in PubMed
8.9field-weighted citation impact, top 2% 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

184 citing papers in PubMed, 271 citations in OpenAlex.

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124 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

2 authors at 2 institutions in 1 country.

Larry M KarnitzDivision of Oncology Research and Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota. Karnitz.larry@mayo.edu.
Lee ZouMassachusetts General Hospital Cancer Center, Department of Pathology, Harvard Medical School, Boston, Massachusetts.
Massachusetts General Hospital · USMayo Clinic · US

Funding

Use of microfluidic tumor cultures to enable clinical trials of therapies for ovarian cancerP50CA136393 · NCI · MAYO CLINIC ROCHESTER · PI Zhenkun Lou · 2009 to 2026
$37.0M
Regulation of the ATR Checkpoint Kinase by DNA DamageR01GM076388 · NIGMS · MASSACHUSETTS GENERAL HOSPITAL · PI ZOU, LEE · 2006 to 2018
$4.3M
ANALYSIS OF A DNA DAMAGE INDUCIBLE CHECKPOINT COMPLEXR01CA084321 · NCI · MAYO CLINIC ROCHESTER · PI KARNITZ, LARRY M · 2000 to 2008
$2.2M
NCI NIH HHS P50 CA136393NCI NIH HHS P50CA136393NCI NIH HHS R01 CA084321NIGMS NIH HHS GM076388NIGMS NIH HHS R01 GM076388
6 · The paper itself

Abstract

The human ATR gene encodes a kinase that is activated by DNA damage and replication stress as a central transducer of a checkpoint signaling pathway. Once activated, ATR phosphorylates multiple substrates, including the kinase Chk1, to regulate cell-cycle progression, replication fork stability, and DNA repair. These events promote cell survival during replication stress and in cells with DNA damage. Accordingly, there has been the tantalizing possibility that ATR inhibitors would be therapeutically useful, especially if they were more effective in tumor versus normal cells. Indeed, multiple studies have demonstrated that alterations that promote tumorigenesis, such as defects in the ATM-p53 pathway, constitutive oncogene activation, and acquisition of the alternative lengthening of telomeres pathway, render tumor cells sensitive to ATR inhibitor monotherapy and/or increase the synergy between ATR inhibitors and genotoxic chemotherapies. Now, nearly two decades after the discovery of ATR, two highly selective and potent ATR inhibitors, AZD6738 and VX-970, are in early-phase clinical trials either as monotherapies or paired with a variety of genotoxic chemotherapies. These trials will generate important insights into the effects of ATR inhibition in humans and the potential role of inhibiting this kinase in the treatment of human malignancies.

Indexed as

Molecular Targeted TherapyAnimalsAntineoplastic AgentsAtaxia Telangiectasia Mutated ProteinsCheckpoint Kinase 1Clinical Trials as TopicDNA DamageHumansNeoplasmsProtein Kinase InhibitorsProtein KinasesSignal TransductionTranslational Research, BiomedicalTreatment OutcomeAntineoplastic AgentsAtaxia Telangiectasia Mutated ProteinsATR protein, humanCheckpoint Kinase 1CHEK1 protein, humanProtein Kinase InhibitorsProtein Kinases

Identifiers

PMID26362996
PMCPMC4631635
OpenAlexW2133106304

What OpenQuestion holds

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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.