ArticlePloS one2013
The anti-melanoma activity of dinaciclib, a cyclin-dependent kinase inhibitor, is dependent on p53 signaling.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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.
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.
Who cites it
34 citing papers in PubMed, 63 citations in OpenAlex.
- Trial
- Post-marketing safety surveillance and adverse event risk factors of abemaciclib: a pharmacoepidemiologic study.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Article
- Medicinal chemistry perspective of pyrido[2,3-RSC advances · 2023Review
- Development of newly synthesised quinazolinone-based CDK2 inhibitors with potent efficacy against melanoma.Journal of enzyme inhibition and medicinal chemistry · 2022Article
- Co-targeting CDK2 and CDK4/6 overcomes resistance to aromatase and CDK4/6 inhibitors in ER+ breast cancer.NPJ precision oncology · 2022Article
- Identification of New Vulnerabilities in Conjunctival Melanoma Using Image-Based High Content Drug Screening.Cancers · 2022Article
- Deep Proteomic Analysis on Biobanked Paraffine-Archived Melanoma with Prognostic/Predictive Biomarker Read-Out.Cancers · 2021Article
- Targeting cell-cycle machinery in cancer.Cancer cell · 2021Review
- Targeting Bfl-1 via acute CDK9 inhibition overcomes intrinsic BH3-mimetic resistance in lymphomas.Blood · 2021Article
- Targeted brachyury degradation disrupts a highly specific autoregulatory program controlling chordoma cell identity.Cell reports. Medicine · 2021Article
- CDK9 activity is critical for maintaining MDM4 overexpression in tumor cells.Cell death & disease · 2020Article
- Rational Combination Therapy for Melanoma with Dinaciclib by Targeting BAK-Dependent Cell Death.Molecular cancer therapeutics · 2020Article
- High-throughput screening identifies candidate drugs for the treatment of recurrent respiratory papillomatosis.Papillomavirus research (Amsterdam, Netherlands) · 2019Article
- Potent Activity of Composite Cyclin Dependent Kinase Inhibition against Hepatocellular Carcinoma.Cancers · 2019Article
- 17-Aminogeldanamycin selectively diminishes IRE1α-XBP1s pathway activity and cooperatively induces apoptosis with MEK1/2 and BRAFApoptosis : an international journal on programmed cell death · 2019Article
- CIC-DUX4 oncoprotein drives sarcoma metastasis and tumorigenesis via distinct regulatory programs.The Journal of clinical investigation · 2019Article
- Benzimidazoles Downregulate Mdm2 and MdmX and Activate p53 in MdmX Overexpressing Tumor Cells.Molecules (Basel, Switzerland) · 2019Article
- Bcl-xScientific reports · 2019Article
- Dinaciclib induces immunogenic cell death and enhances anti-PD1-mediated tumor suppression.The Journal of clinical investigation · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
Although cyclin dependent kinase (CDK)-2 is known to be dispensable for the growth of most tumors, it is thought to be important for the proliferation of melanoma cells, where its expression is controlled by the melanocyte-lineage specific transcription factor MITF. Treatment of a panel of melanoma cells with the CDK inhibitor dinaciclib led to a concentration-dependent inhibition of growth under both 2D adherent and 3D organotypic cell culture conditions. Dinaciclib targeted melanoma cell lines regardless of cdk2 or MITF levels. Inhibition of growth was associated with a rapid induction of G2/M cell arrest and apoptosis. Treatment of human melanoma mouse xenografts with dinaciclib led to tumor regression associated with reduced retinoblastoma protein phosphorylation and Bcl-2 expression. Further mechanistic studies revealed that dinaciclib induces p53 expression whilst simultaneously downregulating the expression of the anti-apoptotic factors Mcl-1 and XIAP. To clarify the role of p53 activation in the dinaciclib-induced cell death, we generated melanoma cell lines in which p53 expression was knocked down using a shRNA lentiviral vector. Knockdown of p53 completely abolished the induction of apoptosis seen following dinaciclib treatment as shown by a lack of annexin-V staining and caspase-3 cleavage. Altogether, these data show that dinaciclib induces apoptosis in a large panel of melanoma cell lines through a mechanism requiring p53 expression.
Indexed as
Identifiers
What OpenQuestion holds
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.