ArticleBritish journal of cancer2020
CDK4/6 inhibition presents as a therapeutic option for paediatric and adult germ cell tumours and induces cell cycle arrest and apoptosis via canonical and non-canonical mechanisms.
Article in British journal of cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 49 citations in OpenAlex.
- Targeting histone deacetylation, cell cycle regulators and heat shock proteins as novel therapeutic strategies for penile cancers.NPJ precision oncology · 2026Article
- Adult Granulosa Cell Tumor With Low-Level Amplifications ofCase reports in urology · 2026Article
- Efficacy and Mechanisms of CDK4/6 Inhibitors in Breast Cancer: Advancing Targeted Therapeutic Strategies.Oncology research · 2026Review
- Epithelial‑mesenchymal plasticity and cisplatin resistance in germ cell tumors: Mechanisms and emerging therapeutic strategies (Review).International journal of oncology · 2025Review
- Ovarian squamous cell carcinoma: clinicopathological features, prognosis and immunotherapy outcomes.Journal of gynecologic oncology · 2025Article
- NSC632839 suppresses esophageal squamous cell carcinoma cell proliferation in vitro by triggering spindle assembly checkpoint-mediated mitotic arrest and CREB-Noxa-dependent apoptosis.Cancer cell international · 2025Article
- Molecular and histopathological characterization of seminoma patients with highly elevated human chorionic gonadotropin levels in the serum.Virchows Archiv : an international journal of pathology · 2024Article
- Novel meriolin derivatives potently inhibit cell cycle progression and transcription in leukemia and lymphoma cells via inhibition of cyclin-dependent kinases (CDKs).Cell death discovery · 2024Article
- Enhancer selectivity across cell types delineates three functionally distinct enhancer-promoter regulation patterns.BMC genomics · 2024Article
- Apoptosis and eryptosis: similarities and differences.Apoptosis : an international journal on programmed cell death · 2024Review
- CD24 targeting with NK-CAR immunotherapy in testis, prostate, renal and (luminal-type) bladder cancer and identification of direct CD24 interaction partners.The FEBS journal · 2023Article
- A Potential Anti-Glioblastoma Compound LH20 Induces Apoptosis and Arrest of Human Glioblastoma Cells via CDK4/6 Inhibition.Molecules (Basel, Switzerland) · 2023Article
- Article
- Brain and Spinal Tumors Originating from the Germ Line Cells.Advances in experimental medicine and biology · 2023Article
- Profiling the 3D interaction between germ cell tumors and microenvironmental cells at the transcriptome and secretome level.Molecular oncology · 2022Article
- Targeting Cell Cycle Progression in HER2+ Breast Cancer: An Emerging Treatment Opportunity.International journal of molecular sciences · 2022Review
- Transcriptional CDK Inhibitors as Potential Treatment Option for Testicular Germ Cell Tumors.Cancers · 2022Article
- Article
- The signal transducer CD24 suppresses the germ cell program and promotes an ectodermal rather than mesodermal cell fate in embryonal carcinomas.Molecular oncology · 2022Article
- Therapeutical interference with the epigenetic landscape of germ cell tumors: a comparative drug study and new mechanistical insights.Clinical epigenetics · 2022Article
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGerm cell tumours (GCTs) are the most common solid malignancies in young men. Although high cure rates can be achieved, metastases, resistance to cisplatin-based therapy and late toxicities still represent a lethal threat, arguing for the need of new therapeutic options. In this study, we analysed the potential of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors palbociclib and ribociclib (PaRi) as molecular drugs to treat cisplatin-resistant and -sensitive paediatric and adult GCTs.
methodsTen GCT cell lines, including cisplatin-resistant subclones and non-malignant controls, were treated with PaRi and screened for changes in viability (triphenyl tetrazolium chloride (XTT) assay), apoptosis rates (flow cytometry, caspase assay), the cell cycle (flow cytometry), the transcriptome (RNA-sequencing, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and on protein level (western blot). Expression profiling was performed on paediatric and adult GCT tissues (expression microarrays, qRT-PCR, immunohistochemistry, 'The Cancer Genome Atlas' database).
resultsWe demonstrate that adult GCTs highly express CDK4, while paediatric GCTs strongly express CDK6 instead. Thus, both GCT types are potentially treatable by PaRi. GCTs presented as highly sensitive towards PaRi, which caused a decrease in viability, cell cycle arrest and apoptosis. Although GCTs mainly arrested in the G1/G0 phase, some embryonal carcinoma cell lines were able to bypass the G1/S checkpoint and progressed to the G2/M phase. We found that upregulation of CDK3 and downregulation of many mitosis regulation factors, like the HAUS genes, might be responsible for bypassing the G1/S checkpoint and termination of mitosis, respectively. We postulate that GCT cells do not tolerate these alterations in the cell cycle and eventually induce apoptosis.
conclusionOur study highlights PaRi as therapeutic options for cisplatin-resistant and -sensitive paediatric and adult GCTs.
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