ArticleOncotarget2015
Efficacy of CDK4 inhibition against sarcomas depends on their levels of CDK4 and p16ink4 mRNA.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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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
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.
- Clinical Utility of CDK4/6 Inhibitors in Sarcoma: Successes and Future Challenges.JCO precision oncology · 2022Pooled it
- Phase II trial of CDK4/6 inhibitor palbociclib in advanced sarcoma based on mRNA expression of CDK4/ CDKN2A.Signal transduction and targeted therapy · 2023Trial
- Osteosarcoma 3D patient derived cultures to test genome-informed personalized treatment options: a feasibility study.Frontiers in medicine · 2026Article
- 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
- Cellular senescence: Neither irreversible nor reversible.The Journal of experimental medicine · 2024Article
- Soft Tissue Sarcomas with Chromosomal Alterations in the 12q13-15 Region: Differential Diagnosis and Therapeutic Implications.Cancers · 2024Review
- Adjuvant Palbociclib May be Associated with Delayed Recurrence in Completely Resected Retroperitoneal Liposarcoma: Results of a Single-Institution Retrospective Cohort Study.Annals of surgical oncology · 2023Article
- CDK4/6-MEK Inhibition in MPNSTs Causes Plasma Cell Infiltration, Sensitization to PD-L1 Blockade, and Tumor Regression.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Treatment of De-Differentiated Liposarcoma in the Era of Immunotherapy.International journal of molecular sciences · 2023Review
- Drugging Hijacked Kinase Pathways in Pediatric Oncology: Opportunities and Current Scenario.Pharmaceutics · 2023Review
- Cellular senescence in cancer: from mechanisms to detection.Molecular oncology · 2021Review
- Empty spiracles homeobox genes EMX1 and EMX2 regulate WNT pathway activation in sarcomagenesis.Journal of experimental & clinical cancer research : CR · 2021Article
- Efficacy of MEK inhibition in a recurrent malignant peripheral nerve sheath tumor.NPJ precision oncology · 2021Article
- Sarcoma stratification by combined pH2AX and MAP17 (PDZK1IP1) levels for a better outcome on doxorubicin plus olaparib treatment.Signal transduction and targeted therapy · 2020Article
- Precision medicine in Ewing sarcoma: a translational point of view.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2020Review
- RABL6A Is an Essential Driver of MPNSTs that Negatively Regulates the RB1 Pathway and Sensitizes Tumor Cells to CDK4/6 Inhibitors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Article
- CDKs in Sarcoma: Mediators of Disease and Emerging Therapeutic Targets.International journal of molecular sciences · 2020Review
- Review
- Sustained Complete Response to Palbociclib in a Refractory Pediatric Sarcoma WithJCO precision oncology · 2020Article
- Use of patient derived orthotopic xenograft models for real-time therapy guidance in a pediatric sporadic malignant peripheral nerve sheath tumor.Therapeutic advances in medical oncology · 2020Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sarcomas are malignant tumors accounting for a high percentage of cancer morbidity and mortality in children and young adults. Surgery and radiation therapy are the accepted treatments for most sarcomas; however, patients with metastatic disease are treated with systemic chemotherapy. Many tumors display marginal levels of chemoresponsiveness and new treatment approaches are needed. Deregulation of the G1 checkpoint is crucial for various oncogenic transformation processes, suggesting that many cancer cell types depend on CDK4/6 activity. Thus, CDK4/6 activity appears to represent a promising therapeutic target for cancer treatment. In the present work, we explore the efficacy of CDK4 inhibition using palbociclib (PD0332991), a highly selective inhibitor of CDK4/6, in a panel of sarcoma cell lines and sarcoma tumor xenografts (PDXs). Palbociclib induces senescence in these cell lines and the responsiveness of these cell lines correlated with their levels of CDK4 mRNA. Palbociclib is also active in vivo against sarcomas displaying high levels of CDK4 but not against sarcomas displaying low levels of CDK4 and high levels of p16ink4a. The analysis of tumors growing after palbociclib showed a clear decrease in the CDK4 levels, indicating that clonal selection occurred in these treated tumors. In summary, our data support the efficacy of CDK4 inhibitors against sarcomas displaying increased CDK4 levels, particularly fibrosarcomas and MPNST. Our results also suggest that high levels of p16ink4a may indicate poor efficacy of CDK4 inhibitors.
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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.