Evidence map›Paper›PMID 27835872›Full record

SynthesisOncotarget2016

Targeting ABCB1 (MDR1) in multi-drug resistant osteosarcoma cells using the CRISPR-Cas9 system to reverse drug resistance.

Tang Liu, Zhihong Li, Qing Zhang, Karen De Amorim Bernstein, Santiago Lozano-Calderon, Edwin Choy, Francis J Hornicek, Zhenfeng Duan

Abstract readMeta-AnalysisReview
In one paragraph

Synthesis in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed, 1 pooled it
–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

46 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  5. Understanding and overcoming multidrug resistance in cancer.Nature reviews. Clinical oncology · 2025
    Review
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  13. Overcoming Multidrug Resistance by Base-Editing-Induced Codon Mutation.ACS pharmacology & translational science · 2023
    Article
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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.

Tang LiuDepartment of Orthopaedics, The 2nd Xiangya Hospital of Central South University, Changsha, Hunan, 410011, P.R. China.
Zhihong LiDepartment of Orthopaedics, The 2nd Xiangya Hospital of Central South University, Changsha, Hunan, 410011, P.R. China.
Qing ZhangDepartment of Orthopaedics, The 2nd Xiangya Hospital of Central South University, Changsha, Hunan, 410011, P.R. China.
Karen De Amorim BernsteinSarcoma Biology Laboratory, Department of Orthopaedic surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
Santiago Lozano-CalderonSarcoma Biology Laboratory, Department of Orthopaedic surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
Edwin ChoySarcoma Biology Laboratory, Department of Orthopaedic surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
Francis J HornicekSarcoma Biology Laboratory, Department of Orthopaedic surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
Zhenfeng DuanSarcoma Biology Laboratory, Department of Orthopaedic surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.

Funding

COMBINATORIAL-DESIGNED NANO-PLATFORMS TO OVERCOME TUMOR DRUG RESISTANCEU01CA151452 · NCI · NORTHEASTERN UNIVERSITY · PI AMIJI, MANSOOR M., DUAN, ZHENFENG · 2010 to 2014
$2.1M
NCI NIH HHS U01 CA151452
6 · The paper itself

Abstract

backgroundMulti-drug resistance (MDR) remains a significant obstacle to successful chemotherapy treatment for osteosarcoma patients. One of the central causes of MDR is the overexpression of the membrane bound drug transporter protein P-glycoprotein (P-gp), which is the protein product of the MDR gene ABCB1. Though several methods have been reported to reverse MDR in vitro and in vivo when combined with anticancer drugs, they have yet to be proven useful in the clinical setting.

resultsThe meta-analysis demonstrated that a high level of P-gp may predict poor survival in patients with osteosarcoma. The expression of P-gp can be efficiently blocked by the clustered regularly interspaced short palindromic repeats (CRISPR)-associated Cas9 system (CRISPR-Cas9). Inhibition of ABCB1 was associated with reversing drug resistance in osteosarcoma MDR cell lines (KHOSR2 and U-2OSR2) to doxorubicin. MATERIALS AND

methodsWe performed a meta-analysis to investigate the relationship between P-gp expression and survival in patients with osteosarcoma. Then we adopted the CRISPR-Cas9, a robust and highly efficient novel genome editing tool, to determine its effect on reversing drug resistance by targeting endogenous ABCB1 gene at the DNA level in osteosarcoma MDR cell lines.

conclusionThese results suggest that the CRISPR-Cas9 system is a useful tool for the modification of ABCB1 gene, and may be useful in extending the long-term efficacy of chemotherapy by overcoming P-gp-mediated MDR in the clinical setting.

Indexed as

CRISPR-Cas SystemsAntibiotics, AntineoplasticATP Binding Cassette Transporter, Subfamily BBone NeoplasmsCell Line, TumorCell ProliferationDose-Response Relationship, DrugDoxorubicinDrug Resistance, MultipleDrug Resistance, NeoplasmGene EditingGene Expression Regulation, NeoplasticHumansOsteosarcomaTransfectionABCB1 protein, humanAntibiotics, AntineoplasticATP Binding Cassette Transporter, Subfamily BDoxorubicinABCB1CRISPR-Cas9meta-analysisosteosarcomaP-glycoprotein

Identifiers

PMID27835872
PMCPMC5347784

What OpenQuestion holds

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Registered trials

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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.