Evidence map›Paper›PMID 35000145›Full record

ArticlePharmacological reports : PR2022

Targeting CDK7 reverses tamoxifen resistance through regulating stemness in ER+ breast cancer.

Yasmin M Attia, Salama A Salama, Samia A Shouman, Cristina Ivan, Abdelrahman M Elsayed, Paola Amero, Cristian Rodriguez-Aguayo, Gabriel Lopez-Berestein

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Article in Pharmacological reports : PR, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.5field-weighted citation impact, top 35% 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

5 citing papers in PubMed, 7 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 2 countries.

Yasmin M Attia *Pharmacology and Experimental Therapeutics Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Kasr Al Eini Street, Fom El Khalig, Cairo, 11796, Egypt. Yasmin.mostafa@nci.cu.edu.eg.
Salama A SalamaPharmacology and Toxicology Department, Faculty of Pharmacy, Al-Azhar University, Cairo, 11651, Egypt. Salama@azhar.edu.eg.ORCID http://orcid.org/0000-0001-6129-6616
Samia A ShoumanPharmacology and Experimental Therapeutics Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Kasr Al Eini Street, Fom El Khalig, Cairo, 11796, Egypt.
Cristina IvanDepartment of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Abdelrahman M ElsayedPharmacology and Toxicology Department, Faculty of Pharmacy, Al-Azhar University, Cairo, 11651, Egypt.
Paola Amero *Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Cristian Rodriguez-AguayoDepartment of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Gabriel Lopez-BeresteinDepartment of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
The University of Texas MD Anderson Cancer Center · USAl-Azhar University · EGCairo University · EG

Funding

NIH HHS FP00000019
6 · The paper itself

Abstract

backgroundAlthough tamoxifen is the mainstay endocrine therapy for estrogen receptor-positive (ER+) breast cancer patients, the emergence of tamoxifen resistance is still the major challenge that results in treatment failure. Tamoxifen is very effective in halting breast cancer cell proliferation; nonetheless, the ability of tamoxifen to target cancer stem and progenitor cell populations (CSCs), a major key player for the emergence of tamoxifen resistance, has not been adequately investigated yet. Thus, we explored whether targeting CDK7 modulates CSCs subpopulation and tamoxifen resistance in ER+ breast cancer cells.

methodsMammosphere-formation assay, stem cell biomarkers and tamoxifen sensitivity were analyzed in MCF7 tamoxifen-sensitive cell line and its resistant counterpart, LCC2, following CDK7 targeting by THZ1 or siRNA.

resultsAnalysis of clinically relevant data indicated that expression of stemness factor, SOX2, was positively correlated with CDK7 expression in tamoxifen-treated patients. Moreover, overexpression of the stemness gene, SOX2, was associated with shorter overall survival in those patients. Importantly, the number of CSC populations and the expression of CDK7, P-Ser118-ER-α and c-MYC were significantly higher in LCC2 cells compared with parental MCF-7 cells. Moreover, targeting CDK7 inhibited mammosphere formation, CSC-regulating genes, and CSC biomarkers expression in MCF-7 and LCC2 cells.

conclusionOur data indicate, for the first time, that CDK7-targeted therapy in ER+ breast cancer ameliorates tamoxifen resistance, at least in part, by inhibiting cancer stemness. Thus, targeting CDK7 might represent a potential approach for relieving tamoxifen resistance in ER+ breast cancer.

Indexed as

Breast NeoplasmsTamoxifenCell Line, TumorDrug Resistance, NeoplasmFemaleGene Expression Regulation, NeoplasticHumansMCF-7 CellsTamoxifenBreast cancerCancer stem cellsCyclin-dependent kinaseSOX2Tamoxifen

Identifiers

PMID35000145
OpenAlexW4206017014

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.