ArticleDiscovery medicine2016
Targeting the cyclin D-cyclin-dependent kinase (CDK) 4/6-retinoblastoma pathway with selective CDK 4/6 inhibitors in hormone receptor-positive breast cancer: rationale, current status, and future directions.
Article in Discovery medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 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
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 86 citations in OpenAlex.
- Clinical Utility of CDK4/6 Inhibitors in Sarcoma: Successes and Future Challenges.JCO precision oncology · 2022Pooled it
- Genomic Profiling of Premenopausal HR+ and HER2- Metastatic Breast Cancer by Circulating Tumor DNA and Association of Genetic Alterations With Therapeutic Response to Endocrine Therapy and Ribociclib.JCO precision oncology · 2021Trial
- Target trial emulation of first-line ribociclib versus palbociclib in hormone receptor-positive, HER2-negative metastatic breast cancer: a comparative effectiveness study.Breast cancer (Tokyo, Japan) · 2026Article
- Next-generation endocrine therapy in HR+/HER2 - breast cancer: oral SERDs, ER-targeting innovations, and ctDNA-driven ESR1 mutation-guided switching.Breast cancer (Tokyo, Japan) · 2026Review
- A 3D Graphene Oxide Model Reveals Fine Particulate Matter Induced Cell Cycle Dysregulation in Neural Stem Cells.Toxics · 2026Article
- Synthesis and Development of Novel Small-Molecule MEIS2 Inhibitors That Induce Cell Death in Breast Cancer Cells by Targeting the Homeobox Domain.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Exploration of Therapeutic Targets Using CDK4 Inhibitors for Head and Neck Mucosal Melanoma.Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery · 2026Article
- The Oncogenic Role of Long Non-Coding RNABiology · 2026Review
- Cyclin-Dependent 4/6 Kinase Inhibitors for Treatment of HER2-Positive Breast Cancer: 2026 Update.Cancers · 2026Review
- Article
- Prognostic Value of Circulating Tumor DNA in HR+/HER2- Stage I-III Breast Cancer: A Systematic Review.Cancers · 2025Review
- Regulation of divergent epithelial-to-mesenchymal transition responses via the CDK4/6-USP51 pathway through ZEB1 protein stabilization.Scientific reports · 2025Article
- Circular RNAs and immunotherapy in retinoblastoma: emerging biomarkers and precision therapeutic strategies.Frontiers in immunology · 2025Review
- Tension-induced adhesion mode switching: the interplay between focal adhesions and clathrin-containing adhesion complexes.bioRxiv : the preprint server for biology · 2024Article
- Improve BBB Penetration and Cytotoxicity of Palbociclib in U87-MG Glioblastoma Cells Delivered by Dual Peptide Functionalized Nanoparticles.Pharmaceutics · 2023Article
- Article
- AKT/mTOR signaling modulates resistance to endocrine therapy and CDK4/6 inhibition in metastatic breast cancers.NPJ precision oncology · 2023Article
- Increased copy number of imprinted genes in the chromosomal region 20q11-q13.32 is associated with resistance to antitumor agents in cancer cell lines.Clinical epigenetics · 2022Article
- Expression patterns and therapeutic implications of CDK4 across multiple carcinomas: a molecular docking and MD simulation study.Medical oncology (Northwood, London, England) · 2022Article
- Hypoxia-induced RBBP7 promotes esophagus cancer progression by inducing CDK4 expression.Acta biochimica et biophysica Sinica · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Dysregulation of the cyclin D-cyclin-dependent kinase (CDK) 4/6-INK4-retinoblastoma (Rb) pathway is an important contributor to endocrine therapy resistance. Recent clinical development of selective inhibitors of CDK4 and CDK6 kinases has led to renewed interest in cell cycle regulators, following experience with relatively non-selective pan-CDK inhibitors that often resulted in limited activity and poor safety profiles in the clinic. The highly selective oral CDK 4/6 inhibitors palbociclib (PD0332991), ribociclib (LEE011), and abemaciclib (LY2835219) are able to inhibit the proliferation of Rb-positive tumor cells and have demonstrated dose-dependent growth inhibition in ER+ breast cancer models. In metastatic breast cancer, all three agents are being explored in combination with endocrine therapy in Phase III studies. Results so far indicated promising efficacy and manageable safety profiles, and led to the FDA approval of palbociclib. Phase II-III studies of these agents, in combination with endocrine therapy, are also underway in early breast cancer in the neoadjuvant and adjuvant settings. Selective CDK 4/6 inhibitors are also being investigated with other targeted agents or chemotherapy in the advanced setting. This article reviews the rationale for targeting cyclin D-CDK 4/6 in hormone receptor-positive (HR+) breast cancer, provides an overview of the available preclinical and clinical data with CDK 4/6 inhibitors in breast cancer to date, and summarizes the main features of ongoing clinical trials of these new agents in breast cancer. Future trials evaluating further combination strategies with CDK 4/6 backbone and translational studies refining predictive biomarkers are needed to help personalize the optimal treatment regimen for individual patients with ER+ breast cancer.
Indexed as
Identifiers
26896604PMC5477652W2275069152What Socratic 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 Socratic graph.