ArticleFrontiers in oncology2021
Palbociclib Induces Senescence in Melanoma and Breast Cancer Cells and Leads to Additive Growth Arrest in Combination With Irradiation.
Article in Frontiers in oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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32 citing papers in PubMed, 61 citations in OpenAlex.
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- Senolytics: charting a new course or enhancing existing anti-tumor therapies?Cellular oncology (Dordrecht, Netherlands) · 2025Review
- TFAP2C-DDR1 axis regulates resistance to CDK4/6 inhibitor in breast cancer.Cancer letters · 2025Article
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- Failure to progress: breast and prostate cancer cell lines in developing targeted therapies.Cancer metastasis reviews · 2024Review
- Reversible and effective cell cycle synchronization method for studying stage-specific investigations.bioRxiv : the preprint server for biology · 2024Article
- Advances in the molecular regulation mechanism of tumor dormancy and its therapeutic strategy.Discover oncology · 2024Review
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- Development of Personalized Strategies for Precisely Battling Malignant Melanoma.International journal of molecular sciences · 2024Review
- Neutrophil-activating secretome characterizes palbociclib-induced senescence of breast cancer cells.Cancer immunology, immunotherapy : CII · 2024Article
- FEN1 Inhibition as a Potential Novel Targeted Therapy against Breast Cancer and the Prognostic Relevance of FEN1.International journal of molecular sciences · 2024Article
- A renal clearable fluorogenic probe for in vivo β-galactosidase activity detection during aging and senolysis.Nature communications · 2024Article
- Autophagy and senescence facilitate the development of antiestrogen resistance in ER positive breast cancer.Frontiers in endocrinology · 2024Review
- Defining melanoma combination therapies that provide senolytic sensitivity in human melanoma cells.Frontiers in cell and developmental biology · 2024Article
- Tumor-specific radiosensitizing effect of the ATM inhibitor AZD0156 in melanoma cells with low toxicity to healthy fibroblasts.Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] · 2023Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionSeveral kinase inhibitors (KI) bear the potential to act as radiosensitizers. Little is known of the radiosensitizing effects of a wide range of other KI like palbociclib, which is approved in ER+/HER2- metastatic breast cancer.
methodIn our study, we used healthy donor fibroblasts and breast cancer and skin cancer cells to investigate the influence of a concomitant KI + radiation therapy. Cell death and cell cycle distribution were studied by flow cytometry after Annexin-V/7-AAD and Hoechst staining. Cellular growth arrest was studied in colony-forming assays. Furthermore, we used C12-FDG staining (senescence) and mRNA expression analysis (qPCR) to clarify cellular mechanisms.
resultsThe CDK4/6 inhibitor palbociclib induced a cell cycle arrest in the G0/G1 phase. Cellular toxicity (cell death) was only slightly increased by palbociclib and not enhanced by additional radiotherapy. As the main outcome of the colony formation assays, we found that cellular growth arrest was induced by palbociclib and improved by radiotherapy in an additive manner. Noticeably, palbociclib treatment clearly induced senescence not only in breast cancer and partly in melanoma cells, but also in healthy fibroblasts. According to these findings, the downregulation of senescence-related FOXM1 might be an involved mechanism of the senescence-induction potential of palbociclib.
conclusionThe effect on cellular growth arrest of palbociclib and radiotherapy is additive. Palbociclib induces permanent G0/G1 cell cycle arrest by inducing senescence in fibroblasts, breast cancer, and melanoma cells. Direct cell death induction is only a minor secondary mechanism of action. Concomitant KI and radiotherapy is a strategy worth studying in clinical trials.
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