Evidence map›Paper›PMID 31012964›Full record

ArticleCancer2019

Activating p53 family member TAp63: A novel therapeutic strategy for targeting p53-altered tumors.

Preethi H Gunaratne, Yinghong Pan, Abhi K Rao, Chunru Lin, Anadulce Hernandez-Herrera, Ke Liang, Antonina S Rait, Avinashnarayan Venkatanarayan, Ashley L Benham, Farwah Rubab and 11 more

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

Article in Cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed, 1 pooled it
1.8field-weighted citation impact, top 13% 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

12 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.

  1. Liposomal delivery of gene therapy for ovarian cancer: a systematic review.Reproductive biology and endocrinology : RB&E · 2023
    Pooled it
  2. Article
  3. Review
  4. Review
  5. How MicroRNAs Command the Battle against Cancer.International journal of molecular sciences · 2024
    Review
  6. Review
  7. Review
  8. Article
  9. Article
  10. 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

21 authors at 7 institutions in 1 country.

Preethi H GunaratneDepartment of Biochemistry and Biology, University of Houston, Houston, Texas.ORCID 0000-0002-6487-3463
Yinghong PanDepartment of Biochemistry and Biology, University of Houston, Houston, Texas.
Abhi K RaoDepartment of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia.
Chunru LinDepartment of Molecular and Cellular Oncology, Division of Basic Science, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Anadulce Hernandez-HerreraLester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas.
Ke LiangDepartment of Molecular and Cellular Oncology, Division of Basic Science, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Antonina S RaitDepartment of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia.
Avinashnarayan VenkatanarayanDepartment of Molecular and Cellular Oncology, Division of Basic Science, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Ashley L BenhamDepartment of Biochemistry and Biology, University of Houston, Houston, Texas.
Farwah RubabSynerGene Therapeutics, Inc., Potomac, Maryland.
Sang Soo KimDepartment of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia.
Kimal RajapaksheDepartment of Molecular and Cell Biology, Baylor College of Medicine, Houston, Texas.
Clara K ChanDepartment of Integrative Biology and Physiology, University of California, Los Angeles, California.
Lingegowda S MangalaGynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Gabriel Lopez-BeresteinCenter for RNAi and Non-Coding RNAs, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Anil K SoodGynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Amy C RowatDepartment of Integrative Biology and Physiology, University of California, Los Angeles, California.
Cristian CoarfaDepartment of Molecular and Cell Biology, Baylor College of Medicine, Houston, Texas.
Kathleen F PirolloDepartment of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia.
Elsa R FloresDepartment of Molecular and Cellular Oncology, Division of Basic Science, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Esther H ChangDepartment of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia.
The University of Texas MD Anderson Cancer Center · USGeorgetown University · USBaylor College of Medicine · USUniversity of California, Los Angeles · US10X Genomics (United States) · USAllogene Therapeutics (United States) · USUPMC Health System · US

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 1985 to 2026
$290.8M
Tissue Culture Shared ResourceP30CA051008 · NCI · GEORGETOWN UNIVERSITY · PI Louis M Weiner · 1990 to 2026
$71.5M
TRAINING GRANT IN TUMOR BIOLOGYT32CA009686 · NCI · GEORGETOWN UNIVERSITY · PI ANNA Tate RIEGEL, DAVID J ROBBINS · 1996 to 2026
$10.8M
Identification of non-coding RNAs to therapeutically target undruggable pathways in metastatic lung adenocarcinoma and squamous cell carcinomaR35CA197452 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI FLORES, ELSA R · 2016 to 2022
$6.4M
Roles of p63 in regulation of miRNA and LincRNA targets in metastatic cancerR01CA160394 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI FLORES, ELSA R · 2012 to 2015
$2.0M
Nanoimmunoliposome-Complexed SPIO: Tumor-Specific Detection of Early Lung CancerR01CA132012 · NCI · GEORGETOWN UNIVERSITY · PI CHANG, ESTHER H, FREEDMAN, MATTHEW T · 2008 to 2010
$1.9M
Significance of Inhibiting Long Non-coding RNAs in Advanced Breast CancerR01CA218025 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI LIN, CHUNRU · 2017 to 2020
$1.5M
Nuclear Architecture, NcRNAs and Epigenetics in Transcriptional Regulation by ERR00DK094981 · NIDDK · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI LIN, CHUNRU · 2013 to 2015
$747k
NCI NIH HHS P30 CA016672NCI NIH HHS P30 CA051008NCI NIH HHS R01 CA132012NCI NIH HHS R01 CA160394NCI NIH HHS R01 CA218025NCI NIH HHS R35 CA197452NCI NIH HHS T32 CA009686NIDDK NIH HHS R00 DK094981
6 · The paper itself

Abstract

backgroundOver 96% of high-grade ovarian carcinomas and 50% of all cancers are characterized by alterations in the p53 gene. Therapeutic strategies to restore and/or reactivate the p53 pathway have been challenging. By contrast, p63, which shares many of the downstream targets and functions of p53, is rarely mutated in cancer.

methodsA novel strategy is presented for circumventing alterations in p53 by inducing the tumor-suppressor isoform TAp63 (transactivation domain of tumor protein p63) through its direct downstream target, microRNA-130b (miR-130b), which is epigenetically silenced and/or downregulated in chemoresistant ovarian cancer.

resultsTreatment with miR-130b resulted in: 1) decreased migration/invasion in HEYA8 cells (p53 wild-type) and disruption of multicellular spheroids in OVCAR8 cells (p53-mutant) in vitro, 2) sensitization of HEYA8 and OVCAR8 cells to cisplatin (CDDP) in vitro and in vivo, and 3) transcriptional activation of TAp63 and the B-cell lymphoma (Bcl)-inhibitor B-cell lymphoma 2-like protein 11 (BIM). Overexpression of TAp63 was sufficient to decrease cell viability, suggesting that it is a critical downstream effector of miR-130b. In vivo, combined miR-130b plus CDDP exhibited greater therapeutic efficacy than miR-130b or CDDP alone. Mice that carried OVCAR8 xenograft tumors and were injected with miR-130b in 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC) liposomes had a significant decrease in tumor burden at rates similar to those observed in CDDP-treated mice, and 20% of DOPC-miR-130b plus CDDP-treated mice were living tumor free. Systemic injections of scL-miR-130b plus CDDP in a clinically tested, tumor-targeted nanocomplex (scL) improved survival in 60% and complete remissions in 40% of mice that carried HEYA8 xenografts.

conclusionsThe miR-130b/TAp63 axis is proposed as a new druggable pathway that has the potential to uncover broad-spectrum therapeutic options for the majority of p53-altered cancers.

Indexed as

Mutation, MissenseAnimalsAntineoplastic AgentsBinding SitesCell Line, TumorCell MovementCisplatinDrug Resistance, NeoplasmFemaleHumansLiposomesMiceMice, NudeMicroRNAsNeoplasm InvasivenessOvarian NeoplasmsAntineoplastic AgentsCisplatinLiposomesMicroRNAsMIRN130 microRNA, humanProtein IsoformsTP53 protein, humanTP63 protein, humanTranscription FactorsTumor Suppressor Protein p53Tumor Suppressor Proteins3-dimensional (3D) spheroidsB-cell lymphoma 2-like protein 11 (BIM)chemosensitizationcisplatinleoyl-sn-glycero-3-phosphatidylcholine (DOPC)microRNA 130b (miR-130b)ovarian cancertransactivation (TA) and N-terminally truncated (ΔN) isoforms of the p63 protein (TAp63/ΔNp63)tumor protein p53tumor-targeted nanocomplex (scL)

Identifiers

PMID31012964
PMCPMC6617807
OpenAlexW2941481974

What OpenQuestion holds

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LicenceCC BY-NC
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.