ArticleEMBO molecular medicine2017
CDK4 phosphorylation status and a linked gene expression profile predict sensitivity to palbociclib.
Article in EMBO molecular medicine, 2017. 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.
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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.
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Who cites it
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.
- Systematic Review of Molecular Biomarkers Predictive of Resistance to CDK4/6 Inhibition in Metastatic Breast Cancer.JCO precision oncology · 2022Pooled it
- CDK4/6 inhibition uncovers subtype-specific vulnerabilities and immune-related responses in esophageal squamous cell carcinoma.Cell death & disease · 2026Article
- Next Frontier in HER2+/HR+ Breast Cancer: Leveraging Cell Cycle Control with CDK4/6 Inhibitors.Journal of personalized medicine · 2026Review
- A comprehensive study integrating bioinformatics analysis and experimental results on HROB as a potential biomarker for the prognosis of lung adenocarcinoma.Scientific reports · 2026Article
- In Silico Analysis of the Role of Estrogen Signaling in the Expression of Metabolic Genes in Breast Cancer.Asian Pacific journal of cancer prevention : APJCP · 2025Article
- Genomic Predictive Biomarkers in Breast Cancer: TheInternational journal of molecular sciences · 2025Review
- Review
- CDK4/6 Inhibitor Resistance in ER+ Breast Cancer.Advances in experimental medicine and biology · 2025Review
- Functional screening reveals genetic dependencies and diverging cell cycle control in atypical teratoid rhabdoid tumors.Genome biology · 2024Article
- Preclinical evaluation of CDK4 phosphorylation predicts high sensitivity of pleural mesotheliomas to CDK4/6 inhibition.Molecular oncology · 2024Article
- CDK4/6 inhibition confers protection of normal gut epithelia against gemcitabine and the active metabolite of irinotecan.Cell cycle (Georgetown, Tex.) · 2023Article
- Firing of Replication Origins Is Disturbed by a CDK4/6 Inhibitor in a pRb-Independent Manner.International journal of molecular sciences · 2023Article
- Review
- Clinical considerations of CDK4/6 inhibitors in HER2 positive breast cancer.Frontiers in oncology · 2023Review
- CDK4 phosphorylation status and rational use for combining CDK4/6 and BRAF/MEK inhibition in advanced thyroid carcinomas.Frontiers in endocrinology · 2023Article
- Differences in metabolic transport and resistance mechanisms of Abemaciclib, Palbociclib, and Ribociclib.Frontiers in pharmacology · 2023Review
- Therapeutic potential of CDK4/6 inhibitors in renal cell carcinoma.Nature reviews. Urology · 2022Review
- CDK4 and CDK6 kinases: From basic science to cancer therapy.Science (New York, N.Y.) · 2022Review
- Monoclonal antibodies to activated CDK4: use to investigate normal and cancerous cell cycle regulation and involvement of phosphorylations of p21 and p27.Cell cycle (Georgetown, Tex.) · 2022Article
- Clinicopathological Features Related to the Efficacy of CDK4/6 Inhibitor-Based Treatments in Metastatic Breast Cancer.Breast cancer : basic and clinical research · 2022Article
Corrections and comments
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Authors and funding
17 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cyclin D-CDK4/6 are the first CDK complexes to be activated in the G1 phase in response to oncogenic pathways. The specific CDK4/6 inhibitor PD0332991 (palbociclib) was recently approved by the FDA and EMA for treatment of advanced ER-positive breast tumors. Unfortunately, no reliable predictive tools are available for identifying potentially responsive or insensitive tumors. We had shown that the activating T172 phosphorylation of CDK4 is the central rate-limiting event that initiates the cell cycle decision and signals the presence of active CDK4. Here, we report that the profile of post-translational modification including T172 phosphorylation of CDK4 differs among breast tumors and associates with their subtypes and risk. A gene expression signature faithfully predicted CDK4 modification profiles in tumors and cell lines. Moreover, in breast cancer cell lines, the CDK4 T172 phosphorylation best correlated with sensitivity to PD0332991. This gene expression signature identifies tumors that are unlikely to respond to CDK4/6 inhibitors and could help to select a subset of patients with HER2-positive and basal-like tumors for clinical studies on this class of drugs.
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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.