Evidence map›Paper›PMID 27225691›Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2016

Maternal Embryonic Leucine Zipper Kinase (MELK) as a Novel Mediator and Biomarker of Radioresistance in Human Breast Cancer.

Corey Speers, Shuang G Zhao, Vishal Kothari, Alyssa Santola, Meilan Liu, Kari Wilder-Romans, Joseph Evans, Nidhi Batra, Harry Bartelink, Daniel F Hayes and 4 more

Open access · bronzeAbstract read
In one paragraph

Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.

0numbers the graph read from it
0cells of the map it votes in
71citing papers in PubMed
6.6field-weighted citation impact, top 3% 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

71 citing papers in PubMed, 133 citations in OpenAlex.

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  9. Targeting MELK in tumor cells and tumor microenvironment: from function and mechanism to therapeutic application.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025
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11 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 2 institutions in 1 country.

Corey SpeersDepartment of Radiation Oncology, University of Michigan, Ann Arbor, Michigan. cspeers@umich.edu.
Shuang G ZhaoDepartment of Radiation Oncology, University of Michigan, Ann Arbor, Michigan.
Vishal KothariDepartment of Radiation Oncology, University of Michigan, Ann Arbor, Michigan.
Alyssa SantolaDepartment of Radiation Oncology, University of Michigan, Ann Arbor, Michigan.
Meilan LiuDepartment of Radiation Oncology, University of Michigan, Ann Arbor, Michigan.
Kari Wilder-RomansDepartment of Radiation Oncology, University of Michigan, Ann Arbor, Michigan.
Joseph EvansDepartment of Radiation Oncology, University of Michigan, Ann Arbor, Michigan.
Nidhi BatraDepartment of Cancer Prevention, MD Anderson Cancer Center, Houston, Texas.
Harry BartelinkNetherlands Cancer Institute, Amsterdam, the Netherlands.
Daniel F HayesClinical Director, Breast Oncology Program, Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan.
Theodore S LawrenceDepartment of Radiation Oncology, University of Michigan, Ann Arbor, Michigan.
Powel H BrownDepartment of Cancer Prevention, MD Anderson Cancer Center, Houston, Texas.
Lori J PierceDepartment of Radiation Oncology, University of Michigan, Ann Arbor, Michigan.
Felix Y FengDepartment of Radiation Oncology, University of Michigan, Ann Arbor, Michigan.
University of Michigan–Ann Arbor · USMichigan Center for Translational Pathology · US

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8M
NCI NIH HHS L30 CA253588NCI NIH HHS P30 CA016672
6 · The paper itself

Abstract

purposeWhile effective targeted therapies exist for estrogen receptor-positive and HER2-positive breast cancer, no such effective therapies exist for triple-negative breast cancer (TNBC); thus, it is clear that additional targets for radiosensitization and treatment are critically needed. EXPERIMENTAL

designExpression microarrays, qRT-PCR, and Western blotting were used to assess MELK RNA and protein expression levels. Clonogenic survival assays were used to quantitate the radiosensitivity of cell lines at baseline and after MELK inhibition. The effect of MELK knockdown on DNA damage repair kinetics was determined using γH2AX staining. The in vivo effect of MELK knockdown on radiosensitivity was performed using mouse xenograft models. Kaplan-Meier analysis was used to estimate local control and survival information, and a Cox proportional hazards model was constructed to identify potential factors impacting local recurrence-free survival.

resultsMELK expression is significantly elevated in breast cancer tissues compared with normal tissue as well as in TNBC compared with non-TNBC. MELK RNA and protein expression is significantly correlated with radioresistance in breast cancer cell lines. Inhibition of MELK (genetically and pharmacologically) induces radiation sensitivity in vitro and significantly delayed tumor growth in vivo in multiple models. Kaplan-Meier survival and multivariable analyses identify increasing MELK expression as being the strongest predictor of radioresistance and increased local recurrence in multiple independent datasets.

conclusionsHere, we identify MELK as a potential biomarker of radioresistance and target for radiosensitization in TNBC. Our results support the rationale for developing clinical strategies to inhibit MELK as a novel target in TNBC. Clin Cancer Res; 22(23); 5864-75. ©2016 AACR.

Indexed as

AnimalsBiomarkers, TumorCell Line, TumorCell ProliferationDisease-Free SurvivalErb-b2 Receptor Tyrosine KinasesFemaleHumansKaplan-Meier EstimateMCF-7 CellsMiceNeoplasm Recurrence, LocalProtein Serine-Threonine KinasesRadiation ToleranceTriple Negative Breast NeoplasmsBiomarkers, TumorErb-b2 Receptor Tyrosine KinasesMELK protein, humanProtein Serine-Threonine Kinases

Identifiers

PMID27225691
PMCPMC8820108
OpenAlexW2405233442

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.