ArticleOncogene2020
ABC-transporter upregulation mediates resistance to the CDK7 inhibitors THZ1 and ICEC0942.
Article in Oncogene, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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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.
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.
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Who cites it
15 citing papers in PubMed, 25 citations in OpenAlex.
- Pharmacological inhibition of CDK7 and CDK9 suppresses gastrointestinal (colon) cancer progression through modulation of stemness, epithelial-mesenchymal transition, and chemoresistance.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Identification of NanoLuciferase Substrates Transported by Human ABCB1 and ABCG2 and Their Zebrafish Homologs at the Blood-Brain Barrier.Molecular pharmacology · 2024Article
- Discovery of bivalent small molecule degraders of cyclin-dependent kinase 7 (CDK7).European journal of medicinal chemistry · 2024Article
- CDK7 in breast cancer: mechanisms of action and therapeutic potential.Cell communication and signaling : CCS · 2024Review
- Super enhancer lncRNAs: a novel hallmark in cancer.Cell communication and signaling : CCS · 2024Review
- Identification of NanoLuciferase Substrates Transported by Human ABCB1 and ABCG2 and their Zebrafish Homologs at the Blood-Brain Barrier.bioRxiv : the preprint server for biology · 2023Article
- The Evolving Pathways of the Efficacy of and Resistance to CDK4/6 Inhibitors in Breast Cancer.Cancers · 2023Review
- Systematic screening identifies ABCG2 as critical factor underlying synergy of kinase inhibitors with transcriptional CDK inhibitors.Breast cancer research : BCR · 2023Article
- Preclinical and Basic Research Strategies for Overcoming Resistance to Targeted Therapies in HER2-Positive Breast Cancer.Cancers · 2023Review
- Progress in the studies on the molecular mechanisms associated with multidrug resistance in cancers.Acta pharmaceutica Sinica. B · 2023Review
- Article
- CDK7/GRP78 signaling axis contributes to tumor growth and metastasis in osteosarcoma.Oncogene · 2022Article
- Research advances in the role and pharmaceuticals of ATP-binding cassette transporters in autoimmune diseases.Molecular and cellular biochemistry · 2022Review
- Pleiotropic Roles of ABC Transporters in Breast Cancer.International journal of molecular sciences · 2021Review
- CDK7 inhibitors as anticancer drugs.Cancer metastasis reviews · 2020Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
The CDK7 inhibitors (CDK7i) ICEC0942 and THZ1, are promising new cancer therapeutics. Resistance to targeted drugs frequently compromises cancer treatment. We sought to identify mechanisms by which cancer cells may become resistant to CDK7i. Resistant lines were established through continuous drug selection. ABC-transporter copy number, expression and activity were examined using real-time PCR, immunoblotting and flow cytometry. Drug responses were measured using growth assays. ABCB1 was upregulated in ICEC0942-resistant cells and there was cross-resistance to THZ1. THZ1-resistant cells upregulated ABCG2 but remained sensitive to ICEC0942. Drug resistance in both cell lines was reversible upon inhibition of ABC-transporters. CDK7i response was altered in adriamycin- and mitoxantrone-resistant cell lines demonstrating ABC-transporter upregulation. ABCB1 expression correlated with ICEC0942 and THZ1 response, and ABCG2 expression with THZ2 response, in a panel of cancer cell lines. We have identified ABCB1 upregulation as a common mechanism of resistance to ICEC0942 and THZ1, and confirmed that ABCG2 upregulation is a mechanism of resistance to THZ1. The identification of potential mechanisms of CDK7i resistance and differences in susceptibility of ICEC0942 and THZ1 to ABC-transporters, may help guide their future clinical use.
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Registered trials
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.