ArticleNature communications2022
CDK12 is hyperactivated and a synthetic-lethal target in BRAF-mutated melanoma.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 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
28 citing papers in PubMed, 38 citations in OpenAlex.
- The Role of Transcriptional and Atypical Cyclin-Dependent Protein Kinases in Melanoma.Cancers · 2026Review
- Uncovering the signaling networks of disseminated glioblastoma cells in vivo with INSIGHT.Nature communications · 2026Article
- IL-37 drives temozolomide resistance in glioblastoma via MAPK pathway activation.Oncology letters · 2026Article
- A genome-scale CRISPRi perturbation atlas of human induced pluripotent stem cells.Nature biotechnology · 2026Article
- PROTAC-based protein degradation: a window of opportunity for melanoma therapy.Journal of biomedical science · 2026Review
- Targeting CDK12/13 Drives Mitotic Arrest to Overcome Resistance to KRASG12C Inhibitors.Cancer research · 2026Article
- CDK12 and CDK13 in oncology: from RNA regulation to therapeutic targeting.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Exploring medicinal mechanism of baicalin in tumor microenvironment of melanoma via bioinformatic and in vitro study.Medical oncology (Northwood, London, England) · 2025Article
- ZDHHC9 promotes osteosarcoma progression via KRAS-associated enhancement of the RAS/MAPK signaling pathway.Scientific reports · 2025Article
- Targeting Transcriptional Cyclin-Dependent Kinases in Cancer.Molecular cancer therapeutics · 2025Review
- Dual Modes of Gene Regulation by CDK12.bioRxiv : the preprint server for biology · 2025Article
- New insights into the dule roles CDK12 in human cancers: Mechanisms and interventions for cancer therapy.Journal of pharmaceutical analysis · 2025Review
- CDK12 inhibition enhances oxaliplatin efficacy in gastric cancer by suppressing the MAPK signaling pathway.Journal of gastrointestinal oncology · 2025Article
- SENP5 drives breast cancer progression through deSUMOYlation of CDK1.Breast cancer research : BCR · 2025Article
- Differential activity of specific inhibitors of transcription regulating cyclin-dependent kinases in thyroid cancer cells.Endocrine-related cancer · 2025Article
- Transcriptional and epigenetic rewiring by the NUP98::KDM5A fusion oncoprotein directly activates CDK12.Nature communications · 2025Article
- Absence of CDK12 in oocyte leads to female infertility.Cell death & disease · 2025Article
- CEP55 Promotes Acral Melanoma Progression via MAPK Pathway and Predicts Survival Following Immunotherapy.Oncology research · 2025Article
- Development of CDK12 as a Cancer Therapeutic Target and Related Inhibitors.Current cancer drug targets · 2025Review
- Development of an orally bioavailable CDK12/13 degrader and induction of synthetic lethality with AKT pathway inhibition.Cell reports. Medicine · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Melanoma is the deadliest form of skin cancer and considered intrinsically resistant to chemotherapy. Nearly all melanomas harbor mutations that activate the RAS/mitogen-activated protein kinase (MAPK) pathway, which contributes to drug resistance via poorly described mechanisms. Herein we show that the RAS/MAPK pathway regulates the activity of cyclin-dependent kinase 12 (CDK12), which is a transcriptional CDK required for genomic stability. We find that melanoma cells harbor constitutively high CDK12 activity, and that its inhibition decreases the expression of long genes containing multiple exons, including many genes involved in DNA repair. Conversely, our results show that CDK12 inhibition promotes the expression of short genes with few exons, including many growth-promoting genes regulated by the AP-1 and NF-κB transcription factors. Inhibition of these pathways strongly synergize with CDK12 inhibitors to suppress melanoma growth, suggesting promising drug combinations for more effective melanoma treatment.
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.