ArticleThe oncologist2021
Cyclin Pathway Genomic Alterations Across 190,247 Solid Tumors: Leveraging Large-Scale Data to Inform Therapeutic Directions.
Article in The oncologist, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled 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.
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, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Clinical Utility of CDK4/6 Inhibitors in Sarcoma: Successes and Future Challenges.JCO precision oncology · 2022Pooled it
- Palbociclib in Solid Tumor Patients With Genomic Alterations in the cyclinD-cdk4/6-INK4a-Rb Pathway: Results From National Cancer Institute-Children's Oncology Group Pediatric Molecular Analysis for Therapy Choice Trial Arm I (APEC1621I).JCO precision oncology · 2024Trial
- CDK2/9 blockade remodels chromatin and drives phenotypic plasticity in glioblastoma organoids.Cell communication and signaling : CCS · 2026Article
- Review
- Copy Number-Based Oncogene Dominance May Suggest ERBB2 Dependence and Trastuzumab Response in HER2-Positive Gastric Cancer.Targeted oncology · 2026Article
- Bioinformatic Analysis to Identify Biomarker Candidates of Complex Karyotype Soft Tissue Sarcomas withBiomolecules & therapeutics · 2026Article
- Postbiotics Combination Synergises the Antiproliferative Effects of Doxorubicin in Gastric Cancer Cells: A Cellular and Molecular Deep Dive.International journal of molecular sciences · 2025Article
- Prioritization of novel agents for further investigation in pediatric non-rhabdomyosarcoma soft tissue sarcomas: A report from the Children's Oncology Group.European journal of cancer (Oxford, England : 1990) · 2025Review
- The landscape of cyclin-dependent kinase 4/6 inhibitors in solid malignancies: emphasis on immunotherapy combinatorial strategies.Medical oncology (Northwood, London, England) · 2025Review
- Capacity for Compensatory Cyclin D2 Response Confers Trametinib Resistance in Canine Mucosal Melanoma.Cancers · 2025Article
- miRNA Differential Expression Profile Analysis and Identification of Potential Key Genes in Active Tuberculosis.Journal of cellular and molecular medicine · 2025Article
- Genetic Screen in a Preclinical Model of Sarcoma Development Defines Drivers and Therapeutic Vulnerabilities.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Comparative Analysis of Comprehensive Genomic Profile in Thymomas and Recurrent Thymomas Reveals Potentially Actionable Mutations for Target Therapies.International journal of molecular sciences · 2024Article
- Combined inhibition of EZH2 and CDK4/6 perturbs endoplasmic reticulum-mitochondrial homeostasis and increases antitumor activity against glioblastoma.NPJ precision oncology · 2024Article
- CDK4/6 Inhibition With Lerociclib is a Potential Therapeutic Strategy for the Treatment of Pediatric Sarcomas.Journal of pediatric surgery · 2024Article
- Article
- Involvement of the tumour necrosis factor receptor system in glioblastoma cell death induced by palbociclib-heptamethine cyanine dye conjugate.Cell communication and signaling : CCS · 2024Article
- Pyrazolo[4,3-International journal of molecular sciences · 2023Article
- Chemomodulatory Effect of the Marine-Derived Metabolite "Terrein" on the Anticancer Properties of Gemcitabine in Colorectal Cancer Cells.Marine drugs · 2023Article
- Comprehensive Landscape of Cyclin Pathway Gene Alterations and Co-occurrence with FGF/FGFR Aberrations Across Urinary Tract Tumors.The oncologist · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundWe describe the landscape of cyclin and interactive gene pathway alterations in 190,247 solid tumors.
methodsUsing comprehensive genomic profiling (315 genes, >500× coverage), samples were analyzed for alterations in activating/sensitizing cyclin genes (CDK4 amplification, CDK6 amplification, CCND1, CCND2, CCND3, CDKN2B [loss], CDKN2A [loss], SMARCB1), hormone genes (estrogen receptor 1 [ESR1], androgen receptor [AR]), and co-alterations in genes leading to cyclin inhibitor therapeutic resistance (RB1 and CCNE1).
resultsAlterations in at least one cyclin activating/sensitizing gene occurred in 24% of malignancies. Tumors that frequently harbored at least one cyclin alteration were brain gliomas (47.1%), esophageal (40.3%) and bladder cancer (37.9%), and mesotheliomas (37.9%). The most frequent alterations included CDKN2A (13.9%) and CDKN2B loss (12.5%). Examples of unique patterns of alterations included CCND1 amplification in breast cancer (17.3%); CDK4 alterations in sarcomas (12%); CCND2 in testicular cancer (23.4%), and SMARCB1 mutations in kidney cancer (3% overall, 90% in malignant rhabdoid tumors). Alterations in resistance genes RB1 and CCNE1 affected 7.2% and 3.6% of samples. Co-occurrence analysis demonstrated a lower likelihood of concomitant versus isolated alterations in cyclin activating/sensitizing and resistance genes (odds ratio [OR], 0.35; p < .001), except in colorectal, cervical, and small intestine cancers. AR and cyclin activating/sensitizing alterations in prostate cancer co-occurred more frequently (vs. AR alterations and wild-type cyclin activating/sensitizing alterations) (OR, 1.79; p < .001) as did ESR1 and cyclin activating/sensitizing alterations in breast (OR, 1.62; p < .001) and cervical cancer (OR, 4.08; p = .04) (vs. ESR1 and cyclin wild-type activating/sensitizing alterations).
conclusionCyclin pathway alterations vary according to tumor type/histology, informing opportunities for targeted therapy, including for rare cancers. IMPLICATIONS FOR PRACTICE: Cyclin pathway genomic abnormalities are frequent in human solid tumors, with substantial variation according to tumor site and histology. Opportunities for targeted therapy emerge with comprehensive profiling of this pathway.
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.