ArticleBiochemical pharmacology2020
Ribociclib mitigates cisplatin-associated kidney injury through retinoblastoma-1 dependent mechanisms.
Article in Biochemical pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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
16 citing papers in PubMed, 28 citations in OpenAlex.
- Matricellular protein SMOC2 safeguards tubular integrity in acute kidney injury via integrin β3-dependent inhibition of CCND1-CDK4/6 axis.Molecular biomedicine · 2026Article
- Acute kidney injury: pathogenesis and therapeutic interventions.Molecular biomedicine · 2025Review
- The regulatory role of CDK4/6 inhibitors in tumor immunity and the potential value of tumor immunotherapy (Review).International journal of molecular medicine · 2025Review
- Drug repurposing of cyclin-dependent kinase inhibitors for neutrophilic acute respiratory distress syndrome and psoriasis.Journal of advanced research · 2025Review
- The deleterious effects of CDK4/6 inhibition on renal recovery post-acute kidney injury.Scientific reports · 2024Article
- Ribociclib leverages phosphodiesterase 4 inhibition in the treatment of neutrophilic inflammation and acute respiratory distress syndrome.Journal of advanced research · 2024Article
- Strategy of combining CDK4/6 inhibitors with other therapies and mechanisms of resistance.International journal of clinical and experimental pathology · 2024Review
- Cellular senescence and kidney aging.Clinical science (London, England : 1979) · 2023Review
- The Therapeutic Potential of CDK4/6 Inhibitors, Novel Cancer Drugs, in Kidney Diseases.International journal of molecular sciences · 2023Review
- Zinc finger protein 24-dependent transcription factor SOX9 up-regulation protects tubular epithelial cells during acute kidney injury.Kidney international · 2023Article
- PFKFB3 mediates tubular cell death in cisplatin nephrotoxicity by activating CDK4.Translational research : the journal of laboratory and clinical medicine · 2023Article
- No safe renal warm ischemia time-The molecular network characteristics and pathological features of mild to severe ischemia reperfusion kidney injury.Frontiers in molecular biosciences · 2022Article
- Kidney toxicity of the BRAF-kinase inhibitor vemurafenib is driven by off-target ferrochelatase inhibition.Kidney international · 2021Article
- A Canadian Study of Cisplatin Metabolomics and Nephrotoxicity (ACCENT): A Clinical Research Protocol.Canadian journal of kidney health and disease · 2021Article
- SOX9 promotes stress-responsive transcription of VGF nerve growth factor inducible gene in renal tubular epithelial cells.The Journal of biological chemistry · 2020Article
- Involvement of the CDKL5-SOX9 signaling axis in rhabdomyolysis-associated acute kidney injury.American journal of physiology. Renal physiology · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Aberrant cell cycle activation is a hallmark of carcinogenesis. Recently three cell cycle targeting cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have been approved for the treatment of metastatic breast cancer. CDK4/6 inhibitors suppress proliferation through inhibition of CDK4/6-dependent retinoblastoma-1 (Rb1) phosphorylation and inactivation, a key regulatory step in G1-to-S-phase transition. Importantly, aberrant cell cycle activation is also linked with several non-oncological diseases including acute kidney injury (AKI). AKI is a common disorder caused by toxic, inflammatory, and ischemic damage to renal tubular epithelial cells (RTECs). Interestingly, AKI triggered by the anti-cancer drug cisplatin can be mitigated by ribociclib, a CDK4/6 inhibitor, through mechanisms that remain unclear. Employing in vivo cell cycle analysis and functional Rb1 knock-down, here, we have examined the cellular and pharmacological basis of the renal protective effects of ribociclib during cisplatin nephrotoxicity. Remarkably, siRNA-mediated Rb1 silencing or RTEC-specific Rb1 gene ablation did not alter the severity of cisplatin-associated AKI; however, it completely abrogated the protective effects conferred by ribociclib administration. Furthermore, we find that cisplatin treatment evokes CDK4/6 activation and Rb1 phosphorylation in the normally quiescent RTECs, however, this is not followed by S-phase entry likely due to DNA-damage induced G1 arrest. The cytoprotective effects of ribociclib are thus not a result of suppression of S-phase entry but are likely dependent on the maintenance of Rb1 in a hypo-phosphorylated and functionally active form under stress conditions. These findings delineate the role of Rb1 in AKI and illustrate the pharmacological basis of the renal protective effects of CDK4/6 inhibitors.
Indexed as
Identifiers
What OpenQuestion 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 OpenQuestion graph.