Article in Journal of the National Cancer Institute, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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.
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
25 authors.
Daniela OttavianiEndocrine Oncology Research Group, Department of Surgery, Royal College of Surgeons in Ireland, University of Medicine and Health Sciences, Dublin, Ireland.ORCID 0000-0001-6573-162X
Mihaela OlaEndocrine Oncology Research Group, Department of Surgery, Royal College of Surgeons in Ireland, University of Medicine and Health Sciences, Dublin, Ireland.ORCID 0000-0003-2612-7678
Alessandra AllottaEndocrine Oncology Research Group, Department of Surgery, Royal College of Surgeons in Ireland, University of Medicine and Health Sciences, Dublin, Ireland.ORCID 0000-0002-7684-2031
Yasmine Maati ChaibiEndocrine Oncology Research Group, Department of Surgery, Royal College of Surgeons in Ireland, University of Medicine and Health Sciences, Dublin, Ireland.
Seán HickeyEndocrine Oncology Research Group, Department of Surgery, Royal College of Surgeons in Ireland, University of Medicine and Health Sciences, Dublin, Ireland.ORCID 0009-0003-2795-8681
Petra JagustEndocrine Oncology Research Group, Department of Surgery, Royal College of Surgeons in Ireland, University of Medicine and Health Sciences, Dublin, Ireland.ORCID 0000-0001-5291-251X
Nicola CosgroveEndocrine Oncology Research Group, Department of Surgery, Royal College of Surgeons in Ireland, University of Medicine and Health Sciences, Dublin, Ireland.ORCID 0000-0002-8296-115X
Sinéad CocchigliaEndocrine Oncology Research Group, Department of Surgery, Royal College of Surgeons in Ireland, University of Medicine and Health Sciences, Dublin, Ireland.ORCID 0000-0002-1596-1950
Fiona BaneEndocrine Oncology Research Group, Department of Surgery, Royal College of Surgeons in Ireland, University of Medicine and Health Sciences, Dublin, Ireland.ORCID 0000-0003-4213-1474
Ramón FallonEndocrine Oncology Research Group, Department of Surgery, Royal College of Surgeons in Ireland, University of Medicine and Health Sciences, Dublin, Ireland.ORCID 0000-0001-5394-7001
Gordon DalyEndocrine Oncology Research Group, Department of Surgery, Royal College of Surgeons in Ireland, University of Medicine and Health Sciences, Dublin, Ireland.ORCID 0000-0001-8976-0839
Aisling HegartyEndocrine Oncology Research Group, Department of Surgery, Royal College of Surgeons in Ireland, University of Medicine and Health Sciences, Dublin, Ireland.ORCID 0000-0002-4514-3334
Lance HudsonEndocrine Oncology Research Group, Department of Surgery, Royal College of Surgeons in Ireland, University of Medicine and Health Sciences, Dublin, Ireland.ORCID 0009-0006-0691-5545
Katherine SheehanEndocrine Oncology Research Group, Department of Surgery, Royal College of Surgeons in Ireland, University of Medicine and Health Sciences, Dublin, Ireland.ORCID 0000-0002-8969-3610
Shannon KalsiEndocrine Oncology Research Group, Department of Surgery, Royal College of Surgeons in Ireland, University of Medicine and Health Sciences, Dublin, Ireland.ORCID 0000-0002-3546-0053
Stephen ShovlinEndocrine Oncology Research Group, Department of Surgery, Royal College of Surgeons in Ireland, University of Medicine and Health Sciences, Dublin, Ireland.ORCID 0000-0002-8692-4719
Aoibhín PowellEndocrine Oncology Research Group, Department of Surgery, Royal College of Surgeons in Ireland, University of Medicine and Health Sciences, Dublin, Ireland.ORCID 0000-0003-1531-5382
Ash BahlCarrick Therapeutics Ltd, Blanchardstown Corporate Park, Dublin, Ireland.
Ed AinscowCarrick Therapeutics Ltd, Blanchardstown Corporate Park, Dublin, Ireland.ORCID 0000-0002-3119-8422
Steffi OesterreichWomen's Cancer Research Center, Magee-Womens Research Institute, UPMC Hillman Cancer Center, Pittsburgh, PA 15213, United States.ORCID 0000-0002-2537-6923
Adrian V LeeWomen's Cancer Research Center, Magee-Womens Research Institute, UPMC Hillman Cancer Center, Pittsburgh, PA 15213, United States.ORCID 0000-0001-9917-514X
Fergus J CouchDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55901, United States.ORCID 0000-0001-9417-9985
Arnold D K HillBeaumont RCSI Cancer Centre, Beaumont Hospital, Dublin, Ireland.ORCID 0000-0001-9617-7983
Damir VarešlijaEndocrine Oncology Research Group, Department of Surgery, Royal College of Surgeons in Ireland, University of Medicine and Health Sciences, Dublin, Ireland.ORCID 0000-0003-1000-0357
Leonie YoungEndocrine Oncology Research Group, Department of Surgery, Royal College of Surgeons in Ireland, University of Medicine and Health Sciences, Dublin, Ireland.ORCID 0000-0002-4904-0367
Funding
Breast Cancer Ireland 18239A01Breast Cancer Now 2019AugSF1310Breast Cancer Now 2021JulyPCC1460Enterprise Ireland IP/2019/0796European Interreg Blue Organoids for Treatment Selection EAPA_0048/2022Irish Research Council SFI-IRC Pathway 22/PATH-S/10866Research Ireland 19/FFP/6443Research Ireland 20/FFP-P/8597Research Ireland 23/SPP/11783Science Foundation IrelandWalk the Walk
6 · The paper itself
Abstract
backgroundCyclin-dependent kinase 12 (CDK12) regulates general gene transcription elongation and plays multiple roles in RNA splicing, DNA damage-response, cell cycle, and genomic stability. However, transcriptional partners that guide CDK12-specific gene programs have not been identified. Genomic alterations in CDK12 have been observed in multiple cancers, exhibiting both pro-tumorigenic and tumor-suppressive functions, suggesting a context-dependent mechanism of action.
methodsCDK12 copy number alterations and gene expression levels were analyzed in matched primary and brain metastatic patient tumors. Clinical significance was assessed by immunohistochemistry in a large cohort of primary breast cancer patient tumors. RNA sequencing, ChIP sequencing, and molecular studies were conducted to explore CDK12's mechanism of action, and pharmacological studies were performed both in vitro and in vivo using models of advanced (endocrine-resistant and metastatic) estrogen receptor positive (ER+) disease.
resultsCDK12 amplifications and gene overexpression were observed in brain metastatic tumors. In ER+ primary patient tumors, high CDK12 protein expression was significantly associated with poor overall survival, particularly within the ER+/HER2-negative group. In ER+ endocrine resistant models, CDK12 regulated estrogen signaling pathways, with ER/MED1 identified as the master transcriptional complex directing CDK12-specific pro-tumorigenic gene programs. Pharmacological inhibition of CDK12 significantly reduced viability in endocrine resistant and metastatic cell and organoid models in vitro, and decreased metastatic spread in vivo.
conclusionThis work describes a novel mechanism for CDK12, suggesting a potential vulnerability in ER+ breast cancer. These findings provide a basis for further investigation into the role of CDK12 inhibition as a therapeutic approach, particularly in advanced disease settings.
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.
Targeting CDK12 disrupts estrogen-receptor chromatin recruitment and ER-MED1 transcription in advanced ER+ breast cancer. · full record | OpenQuestion